Transcript Chapter 5 Chemical messengers

Chapter 5
Chemical Messengers
1.
Mechanisms of Intercellular Communication
細胞間溝通的機制
2.
Chemical Messengers 化學訊息傳導物
3.
Signal Transduction Mechanisms 訊息傳遞機制
4.
Long-Distance Communication via the Nervous
and Endocrine Systems
經由神經及內分泌細胞做長距離的溝通
I. Mechanisms of Intercellular
Communication
 Virtually all body functions require communication 溝通
between cells
 In relatively few instances cells are physically linked by gap
junctions 空隙聯合; in most instances cell communicate
through chemical messengers 化學訊息傳導物


Direct Communication Through Gap
Junctions
Indirect Communication Through
Chemical Messengers
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Direct Communication Through Gap Junctions
Figure 5.1 Types of intercellular
communication. (a) Direct
communication through gap junction.
Gap junctions are composed of
membrane protein structures called
connexons that link the cytosols of
two adjacent cells, allowing ions
and small molecules to move
between cells.
Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings.
 The movement of ions through gap junctions electrically couples the
cells, such that electrical signals in one cell are directly transmitted to the
neighboring cells  for example, in heart muscle, smooth muscle
 The movement of small molecules through gap junctions metabolically
couples the cells, such that one cell can provide necessary nutrients to
other cells  for example, in bone cells
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Indirect Communication Through Chemical
Messengers
Figure 5.1 Types of intercellular
communication. (b) Communication via
chemical messengers. After a secretory
cell 分泌細胞 releases a messenger
訊息物 into the extracellular fluid, the
messenger binds to receptors 接受器
on target cells 目標細胞, triggering a
response in the target cell
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 Most often, cells communicate via chemical messengers, which are all
ligands 結合物, molecules that bind to proteins reversibly
 A target cell responds to the chemical messenger because it has certain
proteins, called receptors 接受器, that specifically recognize and bind the
messenger
 The binding of messengers to receptors produces a response in the target
cell through a variety of mechanisms referred to as signal transduction
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II. Chemical Messengers




Functional Classification 功能分類
of Chemical Messengers
Chemical Classification 化學分類
of Messengers
Synthesis and Release 合成及釋放
of Chemical Messengers
Transport 運送 of Messengers
Functional Classification of Chemical
Messengers
 Chemical messengers can be classified on the basis of their
function 功能 and chemical structure 化學結構
 Although there are hundreds of chemical messengers, most
can be classified into four main categories:
 Paracrines 旁泌素
 Autocrines 自泌素
 Neurotransmitters 神經傳導物質
 Hormones 賀爾蒙
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Paracrine & Autocrine
Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings.
Figure 5.2 Functional
classes of chemical
messengers. (a) Paracrines
are secreted by one cell and
diffuse to a nearby target cell.
(b) Autocrines bind to
receptors on the cell that
secreted them.
 Paracrines generally include growth factors 生長因子, clotting factors
凝血因子, and cytokines 細胞激素  growth factors are proteins that
stimulate proliferation 增生 and differentiation 分化 of cells; clotting
factors are proteins that formation of a blood clot 血塊; cytokines are
peptides, usually released from immune cells 免疫細胞, that function in
coordinating the body’s defense against infection 一同對抗感染
 Autocrines are similar to paracrine, except that autocrines act on the
same cell that secreted them
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Neurotransmitters & Hormones
Figure 5.2 Functional classes of chemical
messengers. (c) Neurotransmitters are secreted from
neurons at functionally specialized structures call
synapses 突觸. The axon terminal of a presynaptic cell
突觸前細胞 releases the neurotransmitter, which then
diffuses a very short distance to bind to receptors on a
very specific target cell called the postsynaptic cell 突觸
後細胞. (d) Hormones are secreted by endocrine cells
into the interstitial fluid. Hormones then diffuse into
bloodstream for transport to target cells in the body.
Target cells are identified by the presence of receptors
for the specific hormone. Cells without receptors for
the hormone cannot respond to the hormone’s signal.
 Neurohormones 神經賀爾蒙 are a special class of
hormones secreted by neurons  like hormones,
they are secreted into the interstitial fluid and then
diffuse into the blood for transport to target cells
throughout the body
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publishing as Benjamin Cummings.
Functional Classification of Chemical
Messengers
 An example of a paracrine messenger is histamine 組織胺, a chemical that
is important in allergic reactions 過敏反應 and inflammation 發炎 and is
secreted by mast cells 肥胖細胞 scattered throughout the body
 Histamine is a biogenic amine 生物性胺類 with paracrine, autocrine, and
neurotransmitter functions
 It is important to realize that one chemical messenger may fit more than
one of these functional classes  ex. histamine, serotonin
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Chemical Classification of Messengers
 A messenger’s chemical structure 化學結構 determines its mechanisms
of synthesis, release, transport and signal transduction
 The most important chemical characteristic is whether the messenger can
dissolve in water or cross the lipid bilayer in the plasma membranes
 Lipophilic 親脂性 (hydrophobic 疏水性)  can cross plasma membrane
 Hydrophilic 親水性 (lipophobic 舒脂性)  can dissolve in plasma or ISF
 The five major classes of chemical messengers:
 Amino acids 胺基酸
 Amines 胺類
 Peptides/proteins 胜肽/蛋白質
 Steroids 類固醇
 Eicosanoids
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Summarize of Chemical classification of Messengers
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Amino Acid Messengers
 Four amino acids are classified as chemical messengers because
they function as neurotransmitters in the brain 腦 and spinal cord 脊髓
 glutamate; aspartate; glycine; GABA (gamma-amino butyric acid)
 Amino acids are lipophobic (hydrophilic) 親水性 they dissolve in
water 溶於水 but do not cross plasma membrane 不能穿越細胞膜
Peptide/Protein Messengers
 Most chemical messengers are polypeptides 多胜肽, chains of
amino acids linked together by peptide bonds
 These messengers are classified as peptides or proteins based on
their size  peptides (< 50 amino acids), proteins (> 50 amino acids)
 Polypeptides are lipophobic  dissolve in water but cannot cross
plasma membranes
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Amine Messengers
 Amines, which are chemical messengers derived from amino acids,
are so named because they all posses an amine group (-NH2)
 Catecholamines 兒茶酚胺—contain a catechol 兒茶酚 group &
derived from tyrosine
 Dopamine 多巴胺  neurotransmitter
 Norepinephrine 正腎上腺素  neurotransmitter
 Epinephrine 腎上腺素  hormone
 Serotonin 血清胺—derived from tryptophan  neurotransmitter
 Histamine 組織胺—derived from histidine  paracrine
 Thyroid hormones 甲狀腺素—derived from tyrosine  hormone
 Most of the amines are lipophobic, but the thyroid hormones are
lipophilic
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Steroid Messengers
 Steroids are a class of compounds derived from cholesterol 膽固醇
 all steroid messengers function as hormones
 Because steroids are derived from cholesterol, which is lipophilic
親脂性, they too are lipophilic and readily cross plasma membrane
容易穿越細胞膜 and are insoluble in water 不溶於水
Eicosanoids
 Most eicosanoids are derived from arachidonic acid 花生四烯酸, a
20-carbon fatty acids that is found in various plasma membrane
phospholipid  include prostaglandins, leukotrienes, and
thromboxanes
 Because eicosanoids are lipids, they readily cross plasma
membrane and are insoluble in water
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Synthesis and Release of Chemical
Messengers
 Synthesis 合成 depends on chemical class
 Release 釋放 of chemical messengers
 Lipophilic messengers  diffusion 擴散
• released upon synthesis 合成後立即釋放
• regulate release by regulating rate of synthesis
藉由調控合成速率來調控釋放
 Lipophobic messengers  exocytosis 胞吐
• stored in vesicles prior to release 釋放前先儲存在小泡中
• regulate rate of exocytosis 藉由調控胞吐的速率來調控釋放
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Amino Acids
 Although amino acids can be obtained from the diet, the four
amino acids that function as neurotransmitters must be
synthesized within the neuron that will secrete them 在欲分泌的神
經細胞內合成
 Following their synthesis in the cytosol 在細胞質合成, amino acid
neurotransmitters are transported into secretory vesicles where
they are stored until they are released by exocytosis
 20 alpha amino acids in body (used in proteins)
 9 are essential 必須的 (身體不可以合成); 11 can be synthesized
in body 身體可以合成
 3/11 are neurotransmitters (glutamate, aspartate, glycine)
 1 gamma amino acid (GABA) = neurotransmitter
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Amines
 All amines are derived from amino acids,
all are synthesized in cytosol by
sequence of enzyme catalyzed reactions
(except thyroid hormones)
 Note that in this pathway, dopamine is the
precursor 前驅物 for norepinephrine,
which in turn serves as the precursor for
epinephrine
 Following synthesis, amines are
packaged into cytosolic vesicles, where
they are stored until their release is
triggered  release occurs by exocytosis
Figure 5.3 Catecholamine synthesis.
Catecholamines are synthesized from the
amino acid tyrosine by a sequence of enzymecatalyzed reactions in which one catecholamine
functions as the precursor for the next. The
names of catecholamines that function as
messengers are highlighted 強調.
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Benjamin Cummings.
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Peptides and Proteins
 Peptides and proteins are synthesized in the same way as other proteins
destined for secretion
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副甲狀腺賀爾蒙
Figure 5.4 Peptide synthesis and release.
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Steroids
 Steroid messengers are
synthesized from cholesterol in a
series of reactions catalyzed by
enzymes located in the smooth ER
or mitochondria 位於平滑內質網或
粒線體上的酵素所催化的反應
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publishing as Benjamin Cummings.
 Because steroids are membranepermeant 膜可滲透, they are
synthesized on demand and
released immediately 依需求而
合成且立即釋放
Figure 5.5 Synthetic pathway for
steroids. Each arrow indicates an
enzyme-catalyzed reaction 酵素催化的
反應. Green boxes indicate hormones
produced in the adrenal cortex 腎上腺
皮質; blue boxes indicate male sex
hormones; orange indicate female sex
hormones
Adrenal cortex
腎上腺皮質
Testes
睪丸
Ovary
卵巢
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Eicosanoids
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publishing as Benjamin Cummings.
 Like steroids, eicosanoids are
synthesized on demand and released
immediately because they are lipophilic
and able to pass through plasma
membranes easily
Figure 5.6 Eicosanoid synthesis.
Phospholipase A2 catalyzes the
conversion of a membrane
phospholipid to arachidonic acid, the
precursor for all eicosanoids.
Arachidonic acid is converted into
eicosanoids via two pathways: The
cyclooxygenase-dependent pathway
leads to the production of
prostaglandins, prostacyclins, and
thromboxanes, whereas the
lipoxygenase-dependent pathway
leads to the production of leukotrienes.
 Prostacyclins and thromboxanes are
important in blood clotting 血液凝固;
prostaglandins are involved in
several systems, including the
inflammatory response 發炎反應
 Leukotrienes also contribute to the
inflammatory response
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Transport of Messenger
 In many instances, the messenger is released from a cell that is near
the target cell, such that the messenger reaches the receptor by
simple diffusion  paracrines; autocrines; most cytokines;
neurotransmitters
 Typically these messengers are quickly degraded in the interstitial
fluid and became inactive, minimizing the spread of their signaling
這種訊息物通常在間質液很快被分解成沒有活性的代謝物，以減少其
訊息擴散出去
 Hormone are transported in the blood and thus have access to most
cells in the body  hormones; neurohormones; some cytokines
 Hormones can be transported in the blood either in dissolved form
溶解態 (hydrophilic 親水性 messengers) or bound to carrier
proteins 結合態 (hydrophobic 疏水性 messengers)
 hydrophilic 親水性 messengers  amines, peptides/proteins
 hydrophobic 疏水性 messengers  steroids, eicosanoids, thyroid
hormone
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Transport of Messengers
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Inc., publishing as Benjamin
Cummings.
Figure 5.7 Transport of messenger in blood.
(a) Hydrophilic messengers, such as peptides and amines,
are secreted by exocytosis, enter the bloodstream, and
dissolve in the plasma. (b) Hydrophobic messengers are
secreted by simple diffusion and then enter the bloodstream.
Most of the messenger molecules are transported bound to
carrier proteins. Only the small amount of free hormone in
the plasma is immediately available binding with target cell
receptors.
 Some carrier proteins are specific for a particular
hormone, such as corticosteroid-binding globulin
(CBG) for cortisol
 Other carrier protein—for example, albumin—are not
specific and can transport many different hormones
 Hormones that are present in dissolved form have
relatively short half-lives 半衰期短, usually minutes
 Hormones that are bound to carrier proteins are
protected from degradation and have longer halflives 半衰期長, generally hours
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Half-life: time it takes for
half of the hormone in
blood to be degraded
III. Signal Transduction
Mechanisms

Chemical messengers transmit their signals by binding to
target cell receptors located either on the plasma
membrane 細胞膜, in the cytosol 細胞質液, or in the
nucleus 細胞核

The location of the receptor depends on whether the
messenger is lipophilic or lipophobic

Properties of Receptors

Intracellular Receptor-Mediated Responses

Membrane-bound Receptor-Mediated Responses
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Properties of receptors
 Receptors shows specificity 專一性 for messenger  they generally
bind only one messenger or a class of messengers
一種接受器通常只會與一種或一大類的傳導物結合
 The binding between a messenger and receptor is a brief, reversible
chemical interaction 傳導物與接受器的結合通常是短暫、可逆的化學反應
 The strength of the binding between a messenger and its receptor is
termed affinity 傳導物與接受器結合的強度稱為親和力
Figure 5.8 Receptor specificity.
Receptor A is specific for
messenger 1, receptor C is
specific for messenger 2, and
neither messenger can bind to
receptor B. Note that receptors
can be located either on the
plasma membrane (A & B) or
inside the cell (receptor C).
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Properties of receptors
Adrenergic receptors  catecholamine (dopamine, epinephrine, norepinephrine)
 Properties:
 Specificity of receptor to messenger  bind only one messenger or
a class of messengers
 Often more than one type of receptor for one messenger
 One cell may different have receptors for different messengers, or
even types of receptors for one messenger
 A single messenger can often bind to more than one type of receptor,
and these receptors may have different affinities 不同親和力 for the
messengers
 epinephrine (adrenaline) and norepinephrine (noradrenaline) can
bind to adrenergic receptors (a1, a2, b1, b2, b3)
 for a receptors: epinephrine = norepinephrine
 for b2 receptors: epinephrine > norepinephrine
 A single target cell may have receptors for more than one type of
messenger  skeletal muscle cells have receptor for acetylcholine and
insulin
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The relationship between receptor binding and the
magnitude of the target cell response

As a general rule, the magnitude of a target cell’s response 目標
細胞反應的大小 to a chemical messenger depends on three factors:
 the messenger’s concentration 傳導物的濃度
 the number of receptors present 接受器的數目
 the affinity of receptor for messenger 傳導物與接受器結合的親和力
 M (messenger)  + R (receptor)  M-R complex   Response 
Figure 5.9 Effect of messenger
concentration on messenger-receptor
binding. The proportion of receptors
bound increases as the concentration
of messenger increases. Because the
amount of bound receptor determines
the magnitude of target cell response,
the y-axis could also have been labeled
“target cell response.”
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The relationship between receptor binding and the
magnitude of the target cell response

The target cell’s response also depends on the number of receptor
it possesses 目標細胞所擁有的接受器數目
M (messenger) +  R (receptor)   M-R complex   Response 
Figure 5.10 Effect of receptor
concentration and affinity on messengerreceptor binding. (a) Effects of receptor
density. The two curves illustrate the effects
of doubling the concentration of a given
receptor on a target cell. R refers to a given
concentration of the receptor, whereas 2R
refers to twice that concentration of that
receptor. When the receptor
concentration doubles, the maximum
number of receptors that can bond with
messenger also doubles.
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The relationship between receptor binding and the
magnitude of the target cell response

The target cell’s response also depends on the affinity of its
receptor for the messenger 接受器與傳導物結合的親和力
M (messenger) + R (receptor)   M-R complex   Response 
Figure 5.10 Effect of receptor concentration
and affinity on messenger-receptor binding.
(b) Effects of receptor affinity. The two
curves illustrate the effects of receptor affinity
on the proportion of receptors with messenger
bound to them. At any concentration of
messenger below saturation, a higher
proportion of high-affinity receptors have
bound messenger compared to low-affinity
receptors. The high-affinity receptors reach
saturation at a lower messenger concentration
than do the low-affinity receptors. Note that
the maximum number of sites that can be
bound is independent of receptor affinity.
接受器被飽和(達最大結合量)與親和力不相關
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Benjamin Cummings.
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Up and Down Regulation of Receptors

The number of receptors that a target cell possesses can vary under
different circumstances as a result of the synthesis of new receptors or
turnover of old receptors 目標細胞擁有的接受器數目會在不同情況下
有所改變，可藉由合成新的接受器或將舊的接受器代謝而增加或減少接受器
的數目

Up-regulation, an increases in the number of receptors compared to
“normal” condition, occurs when cells are exposed to low messenger
concentrations for a prolonged period
當細胞長期暴露在低濃度的傳導物之下，細胞會藉由增加接受器的數目來
適應此狀況，此稱為接受器的上調節作用

By producing more receptors, target cells adapt to the relative lack of
messenger by becoming more responsive to it 因為產生較多的接受器，
目標細胞會對此低濃度的傳導物敏感性增加而適應之

Down-regulation, a decrease in the number of receptors, occurs when
messenger concentrations are higher than normal for a prolonged
period 反之，當長期暴露在高濃度的傳導物之下，細胞可藉由降低接受器
數目而適應之，稱為接受器的下調節作用
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Receptor Agonists and Antagonists
 Although target cell responses are always triggered by receptor
binding, it is not true that receptor binding always triggers a
response 並不是結合物與接受器結合都會誘導反應產生
 Ligands that bind to receptors and produce a biological response
are called agonists 作用劑；致效劑, whereas antagonists 拮抗劑 are
ligands bind to receptors do not produce a response
 Instead, antagonists may actually complete with agonists for the
receptor, decreasing the likelihood that the binding of agonist to
receptor will occur and bring about a response 拮抗劑可與作用劑競爭
而降低作用劑與接受器結合的機會，使其不產生反應
 Norepinephrine is an endogenous ligands 內生性結合物 binding to
an a receptor  phenylephrine is an a agonist and exerts the same
effects, however, phenoxybenzamine is an a antagonist and prevents
norepinephrine from binding to a receptor
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Signal transduction mechanisms for responses
mediated by intracellular receptors

Receptors for lipophilic messengers are usually located in the
cytosol or nucleus of target cells and are readily accessible
because these messengers easily permeate the plasma membrane
脂溶性傳導物的接受器通常位於細胞質或細胞核內，因傳導物很容易
進入細胞膜而接近接受器

The binding of the messenger to the receptor alters the synthesis
of a specific protein  changes in protein synthesis can take hours
or even days, effects of lipophilic messengers are generally slow to
develop 脂溶性傳導物與接受器結合後會影響蛋白質合成，由於蛋白質
的合成需要一段時間，因此脂溶性傳導物的反應比較慢發生

In addition, because these newly synthesized proteins often remain
in the target cells long after the messenger is gone, the effects can
persist a long time 此外，當傳導物離開後，由於期促進合成的蛋白
質還在細胞內產生作用，因此其反應還可維持一段時間
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Figure 5.11 Actions of
lipophilic messengers
on target Cell.

a. When receptors
are in the nucleus, the
hormone diffuses
into the nucleus and
binds to the receptor,
forming a hormonereceptor complex in
the nucleus
Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings.

b. When receptor are in the cytosol, the hormone binds to the receptor
there, forming a hormone-receptor complex that then moves into the
nucleus

The hormone-receptor complex binds to the hormone response element
(HRE), which is located at the beginning of a specific gene   activating (or
deactivating) a gene  mRNA is transcribed in the nucleus

mRNA moves from the nucleus into the cytosol through nuclear pores

mRNA is translated by ribosomes to form proteins  response
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Signal transduction mechanisms for responses
mediated by membrane-bound receptor

Lipophobic messengers cannot permeate the plasma
membrane to any significant degree and thus their receptors
are located on the plasma membrane and face the
extracellular fluid 親水性的傳導物無物法穿越細胞膜，因此接
受器位於細胞膜上，面向細胞外液

The receptors for these messengers fall into three general
categories:

Channel-linked Receptors

Enzyme-linked Receptors

G-Protein-linked Receptors
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Channel-linked Receptors
Voltage-gated channel
 Ion channels that open or close in response to the binding of a
chemical to a receptor or to the channel are called ligand-gated
channels 因結合物結合而使接受器(通道)打開或關閉的離子通道稱為
結合物-閘門通道
 Channel-linked receptors are a type of ligand-gated channel in
which the ligand is a messenger that binds to a receptor
 These channels fall into two categories:
 Fast channels–the receptor and channel are the same protein
 Slow channels–the receptor and channel are separate protein but
are coupled together by a third type of protein, called G protein
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Fast ligand-gated channels
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Figure 5.12 Fast ligand-gated
channels and how they
change the electrical
properties of cells. Binding of
a messenger to the
receptor/channel opens the
ions channel. The opening of
most ion channels results in
movement of ions into or out
of the cell, which changes
the electrical properties of
the cell.
 Because the binding of messenger to receptor is brief, and the
channel is open only while the messenger is bound, the change in
membrane potential does not usually last long and terminates in a few
milliseconds
 For example, the neurotransmitter acetylcholine stimulates skeletal
muscle contraction by binding to nicotinic receptor, which is sodium
channel
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Fast ligand-gated channels
Figure 5.13 Fast ligand-gated
calcium channels. Binding of a
messenger to the receptor/channel
opens calcium channel, enables
calcium ions to enter the cell.
Calcium entry will  change the
electrical properties 改變細胞的電性
of the cell, but calcium also trigger a
variety of responses such as a
 secretion of some product by
exocytosis, muscle contraction,
or  change in activity of a protein.
In the last instance, calcium  acts
as a second messenger, binding to
the protein calmodulin to form a
calcium-calmodulin complex  the
complex activates a protein kinase,
which phosphorylates a protein that
produces a response in the cell.
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



Calcium Levels in Cytosol
 Calcium is well suited for its role in intracellular signaling because
it is normally present in very low concentrations in the cytosol
(10-7 – 10-6 M), as compared to 10-3 M in extracellular fluid
 The significance of this low cytosolic concentration of calcium is
that entry into a cell of even a small quantity of calcium causes a
relatively large percentage change in the concentration, which
means that the system is sensitive
 Intracellular calcium levels are maintained at their normal low
levels by three processes:
 active transport across plasma membrane
 sequestration by binding with proteins in cytosol
 active transport into smooth endoplasmic reticulum or
mitochondria
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Enzyme-Linked Receptors
 Enzyme-linked receptors function both as enzymes and as receptors  are
transmembrane proteins, with the receptor side facing the interstitial fluid and
the enzyme side facing the cytosol
 Most enzyme-linked receptors are tyrosine kinases, other are guanylate
cyclases, which catalyze the conversion of GTP to the second messenger
cGMP
 These enzymes are normally inactive but are activated when a messenger
binds to receptor, which allows them to catalyze intracellular reactions

A messenger binds to the receptor,
changing its conformation   the
conformation change activates the
tyrosine kinase

The tyrosine kinase then catalyzes
phosphorylation of an intracellular
protein   phosphorylation of the
protein changes its activity by
covalent modulation, bringing about a
Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings.
response in the target cell
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Figure 5.14 An enzyme-linked receptor.
G Protein Linked Receptors
 G protein-linked receptors works by activating special membrane
proteins called G proteins
 G protein are located on the intracellular side of the plasma
membrane, where they function as links between the G proteinlinked receptor and other proteins in the plasma membrane, such as
ion channels or enzymes
 G proteins, which get their name from their ability to bind guanosine
nucleotides, have three subunits: alpha (a), beta (b), and gamma (g)
 G proteins are a diverse group  functionally, G proteins can be
classified into three basic types:
 those that affect ion channels  slow ligand-gated ion channels
 stimulatory G proteins (Gs)  activation of enzymes  production
of second messengers 次級訊息傳導物
 inhibitory G proteins (Gi)  inhibition of enzymes  reduction of
second messengers
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Slow ligand-gated ion channel
Figure 5.15 Action of a G protein on a
slow ligand-gated ion channel. 
Binding of a messenger to a G-proteinlinked receptor activates the G protein.
 The alpha subunit moves to an ion
channel in the membrane.  The ion
channel opens or closes, changing the
permeability of the membrane to a
specific ion. The movement of ions across
activate
the plasma membrane is altered,
inactivate
changing the electrical properties of the
cell.
P139 Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings.
 There are two important differences between the fast and slow ligandgated channels:
 At fast ligand-gated channel, messenger bind to receptor only opens the
channel; G protein-linked receptor can be either opened or closed by
messenger binding to the receptor
 Binding of a messenger to channel-linked receptor produces an immediate and
brief (only a few milliseconds) response in the target cell; G protein-linked
receptor are slow and stay open or closed for long periods, often minutes
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G Protein Linked Receptors
 G protein-regulated enzymes are associated with the
production of second messengers in the cytosol
 Five major second messengers account for most of the
communication through G-protein-regulated enzymes:
 cAMP (cyclic adenosine monophosphate)
 cGMP (cyclic guanosine monophosphate)
 Inositol triphosphate (IP3)
First
messenger
 Diacylglycerol (DAG)
 Calcium
Second
messenger
Response
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cAMP second messenger system
 The first messenger binds to the
receptor, activating a Gs protein
 The G protein releases the a
subunit, which binds to and
activates the enzyme adenylate
cyclase
 Adenylate cyclase catalyzes the
conversion of ATP to cAMP
 cAMP activates protein kinase
A, also called cAMP-dependent
protein kinase
 The protein kinase catalyzes the
transfer of a phosphate group
from ATP to a protein, thereby
altering the protein’s activity
 Altered protein activity causes
a response in the cell
Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings.
Figure 5.16 The cAMP second
messenger system.
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Termination of cAMP second messenger system
 Termination of the actions 作用終止 of cAMP requires its
degradation by the enzyme cAMP phosphodiesterase (PDE)
cAMP (activate)
phosphodiesterase (PDE)
AMP (inactivate)
 For the actions of the phosphorylated protein to be terminated,
the phosphate group must be removed by phosphatases
 The concentration of cAMP in a cell is determined by the relative
rates of synthesis (adenylate cyclase) and breakdown
(phosphodiesterase)
 Caffeine, a stimulant found in coffee and other beverages, inhibit
phosphodiesterase, causing levels of cAMP to rise  increase
heart rate 心跳速率增加, wakefulness 不能入睡, and heightened
alertness 警覺性增加
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cGMP second messenger system
 cGMP is a second messenger catalyzed by an enzyme-linked receptor,
guanylate cyclase
 Guanylate cyclase is more commonly associated with G proteins, in
which case the cGMP second messenger system is similar to cAMP
but activates protein kinase G, also called cGMP-dependent protein
kinase
Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings.
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Phosphatidylinositol second messenger system
Figure 5.17 The phosphatidylinositol second messenger system.

The messenger binds to its
receptor, activating a G protein

The G protein releases the a
subunit, which binds to and
activates the enzyme
phospholipase C

Phospholipase C catalyzes the
conversion of a membrane
phospholipid called
phosphatidylinositol 4,5biphosphate (PIP2) to DAG
and IP3, each of which functions
as a second messenger
Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings.

a DAG remains in the membrane and activates the enzyme protein kinase C, a
which catalyzes the phosphorylation of a protein  a bringing about a response
in the cell

b At the same time, IP3 moves into the cytosol  b triggers the release of
calcium from the endoplasmic reticulum  b acts on proteins to stimulate
contraction or secretion; or c acts as a second messenger by binding to
calmodulin, activating a protein kinase that phosphorylates a protein that
produces a response in the cell
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Signal amplification in the cAMP second messenger system
 The ability of small changes
in the concentration of a
chemical messenger to elicit
marked responses in target
cells, a phenomenon known as
signal amplification
 The net result in Figure 5.18 is
that a large number of endproduct molecules can be
regulated in response to the
binding of a single ligand
molecule to its receptor
 Cascade, a series of
sequential steps that
progressively increase in
magnitude  is common in
chemical messenger
systems and account for much
of the signal amplification
that occurs
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Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings.
Figure 5.18 Signal amplification, in this
case by the second messenger cAMP.
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V. Long Distance Communication via the
nervous and endocrine systems
 The body has two organ systems specialized for long-distance communication:
the nervous system 神經系統 and the endocrine system 內分泌系統
 The endocrine system communicates through chemicals called hormones,
which travel via the bloodstream to virtually all cells in the body
 Hormones generally communicate by altering protein synthesis or activating
G proteins, processes that are considerably slower than electrical and
chemical signal used by the nervous system
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Signal Transmission in Neurons
 The nervous system consists of
neurons 神經細胞 and
supporting cells 支撐性細胞
called glial cells 膠細胞
 Neurons are capable of
communicating long distance, first
by transmitting electrical signals
along the length of the cell, and
then by transmitting chemical
signals through the release of a
neurotransmitter at a synapse
 Signal transmitted by the
nervous system travel quickly
and are generally of short
duration, making the system ideal
for controlling movements and
monitoring the world around us
Copyright © 2008 Pearson Education, Inc., publishing as Benjamin Cummings.
Figure 5.19 Signal transmission in
neuron. Neurons transmit both electrical
signals within the cell and chemical
signals between cells.
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