Transcript Synaptic receptors, neurotransmitters and brain modulators

Physiology of visceral and
neurohumoral regulations
Romana Šlamberová, MD PhD
Department of Normal,
Pathological and Clinical
Physiology
Introduction
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Slides from the lecture.
Respecting the copyrights it was not
possible to publish pictures showed at the
lecture at our website.
© 2007, Romana Slamberova, MD PhD
Autonomic nervous system (1)
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The autonomic nervous system (ANS) or
visceral nervous system is the part of the
peripheral nervous system that controls
homeostasis.
The main systems that are controled by the
ANS are cardiovascular, GIT and respiratory.
Many of the activities of the ANS are
involuntary. (However, breathing, for example,
can be in part consciously controlled.)
Autonomic nervous system (2)
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The ANS may be
defined: Part of the
nervous system,
which controls
smooth muscles,
visceras and glands.
These neurons form
reflex arcs that pass
through the lower
brainstem or medulla
oblongata.
This explains that when
the CNS is damaged
above that level, a
vegetative life is still
possible, whereby
cardiovascular,
digestive and
respiratory functions
are adequately
regulated.
Reflex arc of the ANS
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Similar as the reflex arc:
receptors in sense organs - afferent
neuron – synapse - efferent neuron
- neuromuscular junction – muscle
BUT, while the somatic efferent
pathway has only one neuron, the
autonomic efferent pathway has 2
neurons.
2 neuronal efferent pathway
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PREGANGLIONIC NEURONS are located in the
brain stem or in the spinal cord.
Their axons are part of the cranial nerves or leaving
ventral root of the spinal cord.
They make a SYNAPSE with the
POSTGANGLIONIC NEURONS, which are located
in autonomic ganglions or in the wall of the goal
organ.
Autonomic efferent pathways are divided to:
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PARASYMPATHETIC DIVISION = craniosacral part
(Cranial nerves and spinal nerves S2-S4)
SYMPATHETIC DIVISION = thoracolumbal part (Spinal
nerves Th1-L2-4)
Ending of the efferent pathway
of the ANS
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The end of the
postganglionic
axon has lots of
terminals with
vesicals with
mediators and
making many
junctions and
synapses and the
mediator is going
to the goal organ.
Mediators of the efferent
pathway
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Cholinergic division of the autonomic nervous system =
mediator ACETYLCHOLIN
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all preganglionic neurons (sympathetic and parasympathetic) =
Nicotinic receptors (ionotropic receptors, not possible to block with
atropin, particularly responsive to nicotine)
all parasympathetic postganglionic neurons = Muscarinic receptors
(metabotropic receptors, possible to block with atropin, particularly
responsive to muscarine)
some of the sympathetic postanglionic neurons (sweat gland, smooth
muscles of the capillary in the skeletal muscles)
Adrenergic division of the autonomic nervous system =
mediator NOREPINEPHRINE
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other sympathetic postganglionic neurons = Alpha receptors
(vasoconstriction), Beta receptors (excitation of the heart)
Cells of medulla of the adrenals were developed as postganglionic
neurons of the sympaticus.
Do you know?
Fly agaric
Amanita muscaria from which
muscarine was isolated
Acetylcholine
Norepinephrine
Function of the ANS (1)
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Sympathetic and parasympathetic divisions typically
function in opposition to each other.
For an analogy, one may think of the sympathetic
division as the accelerator and the
parasympathetic division as the brake.
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The sympathetic division typically functions in actions
requiring quick responses.
The parasympathetic division functions with actions that do
not require immediate reaction.
Consider sympathetic as "fight or flight" and
parasympathetic as "rest and digest".
Function of the ANS (2)
Sympathetic division
Parasympathetic division
↑ heart rate
↓ heart rate
↑ contractility
↓ contractility
↑ conduction velocity
↓ conduction velocity
vasoconstriction
vasodilatation
vasodilatation in skeletal muscles
vasoconstriction of coronary
arterionles
Lungs
dilatation
Contraction
Eyes
mydriasis (contraction of m. dilator
pupillae)
miosis
GIT
↓ motility of the stomach and
intestines
↑ motility of the stomach and
intestines
↑ tonus of sphincters
↓ tonus of sphincters
Heart
Arteries and veins
Skin
↑ sweating (palms of hands)
contraction of pilomotor muscles
Male sex organs
Ejaculation
Erection
Sympathetic nervous system
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Diverts blood flow away from the GIT and skin via
vasoconstriction.
Blood flow to skeletal muscles, the lung is enhanced
(by as much as 1200%, in the case of skeletal
muscles).
Dilates bronchioles of the lung, which allows for
greater alveolar oxygen exchange.
Increases heart rate and the contractility of cardiac
cells (myocytes), thereby providing a mechanism for
the enhanced blood flow to skeletal muscles.
Dilates pupils and relaxes the lens, allowing more
light to enter the eye.
Parasympathetic nervous
system
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Dilates blood vessels leading to the GIT, increasing
blood flow. This is important following the
consumption of food, due to the greater metabolic
demands placed on the body by the gut.
Stimulates salivary gland secretion, and accelerates
peristalsis, so, in keeping with the rest and digest
functions, appropriate PNS activity mediates digestion
of food and indirectly, the absorption of nutrients.
Constricts the bronchiolar diameter when the need for
oxygen has diminished.
Constriction of the pupil and lens.
Is also involved in erection of genitals, via the pelvic
splanchnic nerves 2-4.
Nicotinic acetylcholine
receptor
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ionotropic receptors that form ion
channels in cells' plasma membranes.
they may be activated by the
neurotransmitter acetylcholine (ACh),
but also by nicotine.
Their action is inhibited by curare
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Curare is an example of a non-depolarizing
muscle relaxant, which blocks the nicotinic
receptors.
Curare has also been used historically as a
paralyzing poison by South American
indigenous people. The prey was killed by
asphyxiation as the respiratory muscles
were unable to contract resulting in apnea.
Muscarinic acetylcholine
receptor
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Metabotropic membrane-bound that use G proteins as their
signalling mechanism.
are more sensitive to muscarine than to nicotine.
By the use of selective radioactively-labelled agonist and
antagonist substances, four subtypes of muscarinic receptors
have been determined, named M1-M5.
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M1 - are found mediating slow EPSP at the ganglion in the
postganglionic nerve, is common in secretory glands (exocrine
glands).
M2 - are found in cardiac tissue and cause a slowing of sinoatrial
depolarization and a decrease in conduction velocity.
M3 – are found on smooth muscles, endocrine and in exocrine
glands. They generally cause smooth muscle contraction and
increased glandular secretions.
Adrenergic receptor
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Metabotropic G protein-coupled receptors.
Subtypes:
 α receptors
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α1: noradrenaline≥ adrenaline; Smooth muscles - in blood vessels
the principal effect is vasoconstriction (the most in the skin and GIT)
α2: adrenaline > noradrenaline; Pre- and postsynaptic nerve
terminals. Mediates synaptic transmission.
β receptors
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β1: noradrenaline > adrenaline; Heart and cerebral cortex. In heart,
agonists enhance myocardial contractility and increase heart rate.
β2: adrenaline > noradrenaline; Lung, smooth muscle, cerebellum,
skeletal muscle. Agonists can be useful in treating asthma. In smooth
muscle, relaxes walls.
β3: noradrenaline > adrenaline; Adipose tissue. Agonists enhance
lipolysis.
Enteric nervous system (1)
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The enteric nervous system (ENS) is the part of the nervous
system that directly controls the GIT.
It is capable of autonomous functions such as the coordination
of reflexes (it may function independently of the CNS, but it is
regulated by the CNS).
It receives considerable innervation from the autonomic
nervous system (often considered a part of ANS).
The neurons of the ENS are collected into two types of ganglia:
myenteric (Auerbach's) and submucosal (Meissner's) plexuses.
It is composed of:
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local sensory neurons that register alterations in the tension of the
gut wall and the chemical environment,
interneurons and motor neurons that control the muscles of the gut,
vasculature and the secretory activity.
Enteric nervous system (2)
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Myenteric Auerbach's plexus
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Located between the longitudinal and circular layers of muscularis
externa in the GIT
Provides motor innervation to both layers and secretomotor innervation
to the mucosa.
It arises from cells of parasympathetic nucleus of the nervus vagus.
Submucosal Meissner's plexus
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is derived, and is formed by branches which have perforated the
circular muscular fibers.
lies in the submucous coat of the intestine
it contains ganglia from which nerve fibers pass to the muscularis
mucosae and to the mucous membrane.
The nerve bundles of the submucous plexus are finer than those of the
myenteric plexus.
Adrenal medulla
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Large quantities of epinephrine and norepinephrine
released into circulation.
Their effect is long-lasting since they are removed
from the circulation slowly.
The effects are the same as the effects of the
sympathetic system.
There are some differences between the effects of
epinephrine and norepinephrine:
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Epinephrine stimulates the heart, whereas
norepinephrine constricts the muscle capillaries.
Epinephrine has 5 - 10 times more effect on tissue
metabolism than norepinephrine.
Control of the ANS
A hierarchy of levels of integration
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Simple reflexes are integrated in the spinal cord.
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More complex reflexes are integrated mainly in the medulla: respiration, heart
rate, blood pressure, swallowing, coughing, sneezing, gagging, vomiting.
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The hypothalamus also controls several autonomic responses.
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There is probably no localized parasympathetic center in hypothalamus.
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Stimulation of the lateral hypothalamus induces several sympathetic
reactions, such as a rise in the blood pressure, pupillary dilation, piloerection,
and others.
Low-voltage stimulation of the middorsal nuclei causes vasodilation in muscles
with vasoconstriction in the skin.
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Stimulation of the dorsomedial nuclei and posterior hypothalamic area produces
increased secretion of catecholamines from adrenal medulla.
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Most of these reactions accompany rage, anger and other emotional responses.
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Hypothalamus projects to the nuclei of the brain stem and the spinal cord that
act on the preganglionic autonomic neurons.
Many regions of the brain control hypothalamus: the cerebral cortex, the
hippocampus, the entorhinal cortex, parts of the thalamus, basal ganglia,
cerebellum, and the reticular formation.
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The nucleus of the solitary
tract
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The major coordinating center for
autonomic functions.
It controls simple autonomic functions
by a set of reflex circuits.
Sensory fibers from the heart, lungs,
GIT project to specific subnuclei in a
viscerotopic manner.
It coordinates elaborate homeostatic
adjustments by transmitting
information from autonomic targets to
both lower (brain stem and spinal cord) and
higher (the amygdala, paraventricular nucleus of
hypothalamus, bed nucleus of the stria terminalis)
brain regions and gets feedback from
there.
The Hypothalamus (1)
A division of the diencephalon
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It sub serves 3 major systems:
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AUTONOMIC NERVOUS SYSTEM
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ENDOCRINE SYSTEM
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LIMBIC SYSTEM
11 important nuclei:
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MEDIAL PREOPTIC NUCLEUS
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Regulates the release of gonadotropic hormones from the Adenohypophysis
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SUPRACHIASMIC NUCLEUS
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Receives input directly form the retina.
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Plays a role in regulating circadian rhythm
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ANTERIOR NUCLEUS
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Important in temperature regulation
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Stimulates PNS
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It’s destruction results in hyperthermia
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PARAVENTRICULAR NUCLEUS
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Synthesizes ADH- and thus regulates water balance
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Releases oxytocin
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Projects directly to autonomic nuclei of brain stem and all spinal cord levels
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The Hypothalamus (2)
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SUPRAOPTIC NUCLEUS
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DORSOMEDIAL NUCLEUS
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Lesions (in Wernicke’s Encephalopathy patients) are associated with thiamine deficiency
and alcoholicism
POSTERIOR HYPOTHALAMIC NUCLEUS
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Contains neurons that produce factors that stimulate or inhibit action of hypothalamus
Contains neurons that produce Dopamine
MAMILLARY NUCLEUS
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Is the satiety center- this means that once it is stimulates, it inhibits the urge to eat
ARCUATE (INFUNDIBULAR) NUCLEUS
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When stimulated in animals, causes savage behaviour!
VENTROMEDIAL NUCLEUS
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Synthesizes ADH- and thus regulates water balance
Releases oxytocin
Plays a role in thermoregulation
Lesion results in poikilothermia
LATERAL HYPOTHALAMIC NUCLEUS
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Induces eating
Hypothalamic nuclei
Function of the hypothalamus
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AUTONOMIC
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THERMOREGULATION
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Stimulation of ANTERIOR HYPOTHALAMUS: regulates and maintains
temperature
Stimulation of POSTERIOR HYPOTHAMUS: produces and conserves heat
WATER BALANCE
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Stimulation of the ANTERIOR HYPOTHALAMUS: excitatory effect on
parasympathetic system
Stimulation of POSTERIOR HYPOTHALAMUS: excitatory effect of
sympathetic system
Paraventricular nuclei synthesize ADH and control kidney water excretion
FOOD INTAKE
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Stimulation of VENTROMEDIAL NUCLEUS inhibits the urge to eat
Stimulation of LATERAL HYPOTHALAMIC NUCLEUS induces the urge to
eat
Cardiovascular system
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The baroreceptor reflex regulates the blood pressure
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The sympathetic system stimulates the heart rate and contractility,
mainly through β adrenergic responses.
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the carotid sinus are stretched by high blood pressure
the signals are transmitted to the brain stem
they inhibit the sympathetic innervation of the heart
activate the parasympathetic innervation.
The long-lasting calcium current is enhanced by norepinephrine,
contributing to an increased force of contraction. This is mediated by cAMP.
also the potassium current is increased.
The parasympathetic regulation decreases heart rate and cardiac
contractility (negative inotropic effect).
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Acetylcholine acts on muscarinic receptors in the SA and AV nodes.
It increases the resting potassium conductance,
this leads to hyperpolarization of sinoatrial cells.
It also increases the threshold for activation and decreases heart
rate.
The pupillary light reflex
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The eye pupil is controlled jointly by sympathetic and
parasympathetic innervation of the two muscles of the
iris.
The parasympathetic postganglionic fibers from the
ciliary ganglion innervate the pupillary sphincter.
Sympathetic fibers from the superior cervical
ganglion innervate the pupillary dilator muscle.
During the light reflex, the parasympathetic input is
activated and the sympathetic input is inhibited,
causing a net decrease in pupillary diameter.
Salivary glands
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The inputs do not exert opposite effects on all
aspects of the salivary gland function.
Sympaticus produces a more viscous
secretion with high amylase activity.
Parasympaticus produces a more watery
saliva.
Urinary bladder
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Controlled by both the sympathetic and the parasympathetic system
following distension of their wall.
voluntary muscles are also involved.
systems are activated by reflexes at the spinal and supraspinal
levels.
The excitatory input to the bladder wall that causes contraction is
parasympathetic.
 Cholinergic axons originate in the intermediolateral region of
the sacral spinal cord
 Acetylcholine acts on muscarinic receptors.
Sympathetic innervation counteracts the parasympaticus.
 The fibers originate in the thoracic and lumbal spinal cord
 The muscles of the bladder wall relax.
Motor neurons of the sacral spinal cord innervate the external
sphincter and cause contraction.
The Vomiting
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integrates somatic and visceral components.
It is induced by the impulses from the
gastrointestinal mucosa to the vomiting center
through the vagus and sympaticus.
Vomiting center is also affected by the
emotions controlled by the limbic system.
Certain chemical agents may stimulate the
vomiting center through the area postrema of
the medulla.
Mass discharge
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The sympathetic system often functions as a unit =
mass discharge = an alarm or stress response =
fight or flight response
The following responses, enhancing vigorous muscle
activity, take place simultaneously:
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increased blood pressure
increased blood flow to the muscles
increased cellular metabolism
increased plasma glucose
increased glycogen degradation
increased muscle strength
increased mental activity
increased rate of blood coagulation
Localized discharge
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Sometimes, sympathetic activation occurs in
isolated portions of the system:
in the temperature regulation
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local heating of the skin
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may cause only a local response
during exercise
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sweating and increased blood flow is present only in the skin
only the blood vessels of the muscles are dilated
responses of the GIT
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only have a local character, without the participation of the
spinal cord