Transcript AP151 Neurotransmitters

NT’s, Receptors and their actions
• Cholinergic Receptors (receptors that respond to Ach)
– Nicotinic
– Muscarinic
• Adrenergic Receptors (receptors that respond to NE)
– Alpha
– Beta
Other NT
Dopamine, serotonin, GABA, Glutimate
• Binding of NT to receptors on post synaptic
membrane can cause EPSPs or IPSPs depending on
the combination of NT and receptor at any given
synapse.
Acetylcholine (ACh)
Used extensively in PNS and in restricted areas of CNS
•Autonomic ganglia,
•Neuromuscular junctions
•Post ganglionic Parasympathetic
neurons
Broken down by Achase
Two types of receptors
1. Nicotinic
2. muscarinic
Nicotinic (Cholinergic) Receptors — Activated by ACh:
• Ionotropic: activation directly leads to movement of ions across membrane
• Chemical (ligand) gated channels
ACh bind receptors/gated channel  channel opens  Na+ flows in  depolarization
• Excitation (EPSP)
Fig. 7.27
Muscarinic (Cholinergic) Receptors—Activated by ACh:
• Metabotropic: binding of receptors directly leads to chemical reactions (metabolism)
• Activates a second-messenger; G-protiens
ACh binds receptor  G protien is activated  G protien signals gated channel  next step varies
• If G protien opens K+ channels: ↑ K+ outflow  hyperpolarization  IPSP
• If G protein closes Ca+ or Na+ channels:
↓ Ca+/Na+ flow into cell  hyperpolarization  IPSP
• if G protein closes (blocks) K+ channels: ↓ K+ leaking  depolarization  EPSP
Can also
close K+
channel in
other cases
Fig. 9.11
Or reduce Ca+
inflow
Norepinephrine (NE) and Epinephrine (E)
• Monoamine > catecholamine
• broken down by monoamine oxidases (MOA)
• Used in sympathetic post-ganglionic neurons and in
some CNS areas.
Fig. 7.31
Adrenergic Receptors (NE, E)
•Metabotropic; binding of receptor initiates metabolic reactions
NE binds receptor  G-protein activates  adenylate cyclase  cAMP  kinase
 open/closes channel (and/or intracellular effects)  IPSP or EPSP
or epinephrine
Changes
in nucleus
And/or activates proteins
within the cytoplasm,
and/or initiates events in
the nucleus
Fig. 9.1
Fig. 9.7
muscarinic
e.g., smooth muscle
effects, increases digestive
activity, slow heart rate ,
gland secretion
Receptor Type
Neurotransmitter
Sensativity
Effector
Effect on Effector
Nicotinic
Ach
Skeletal muscle,
adrenal medulla,
post-gangioloic
neurons of ANS
Excitatory
Muscarinic
Ach in PD-ANS
Cardiac muscle,
smooth muscle,
exocrine glands,
some endocrine
glands
Excitatory or
inhibitory
Alpha-1
Norepinephrine >
epinephrine
Most sympathetic
target tissues
excitatory
Alpha-2
Norepinephrine >
epinephrine
Digestive organs
inhibitory
Beta-1
Norepinephrine =
epinephrine
Heart
excitatory
Beta-2
Epinephrine only
Smooth muscle of
arterioles and
bronchioles
Inhibitory (i.e., leads
to dilation)
Table 7.5
CASTOR BEANS
CASTOR BEANS
MM
How various substances influence neuron and synaptic function
• Review of ANS neurons and NT’s
Dopamine
• In CNS
• Can be excitatory or inhibitory
• 2 major dopamine systems in brain
– Involved with motor control (involved with inhibiting
muscles that should be relaxed/preventing overstimulation
of skeletal muscle)
• Basal Nuclei (nigrostriatal system)
– involved in behavior and emotional reward (“feel good” NT)
• Part of reward system that influences behavior (“is it worth it to
choose a course of action)
• Most addictions activate this system, also risk taking behaviors
• Overactivity contributes to schizophrenia
– Which is treated by anti-dopamine drugs
• Mesolimbic dopamine system
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Serotonin
• In CNS (and enteric system/GI tract)
• Excitatory and inhibitory
• Involved in regulation of mood, behavior, appetite and cerebral
circulation, muscle control, bone remodelling, reproductive
behavior.
• Effects mood, perception, and behavior
– Linked to depression
• LSD is structurally similar
• Ecstasy targets serotonin receptors
• SSRIs (serotonin-specific reuptake inhibitors) are
antidepressants
– e.g., Prozac, Zoloft, Paxil, Luvox
– Block reuptake of serotonin, prolonging its action
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GABA (gamma-aminobutyric acid)
• Inhibitory (opens Cl- channels)
• is most common NT in brain
• Inhibits neural pathways (so they are not overactive)
• Linked to anxiety levels (increased GABA
reduces axiety)
• Barbituates & Benzodiazepines (Xanax and
valium) are agonists of GABA receptors
• Alcohol also targets GABA receptors
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Glutamate
• Glutamate most important excitatory NT in CNS
• Important in memory formation and learning
• Involved with excitotoxicity
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Glycine
• Inhibitory (mostly within brainstem and spinal
cord)
• Important in maintiaing proper balance of
inhibition and excitation that controls skeletal
muscle contraction
– Opens Cl- channels which hyperpolarize
– Strychnine blocks glycine receptors
• Causes spastic paralysis (over active
stimulation/excitation of skeletal muscle)
7-69
• Interesting concept—NOT fact checked