Autonomic Nervous System (ANS)
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2.
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Connects the CNS to internal body organs
Involuntary control – breathing, heart contraction, food digestion etc.
Innervates cardiac and smooth muscles, most exocrine and some endocrine glands, fat
Based on gender, age and ethnicity
Somatic Nervous System – voluntary control, innervates muscles, only NT is acetylcholine
ANS has two branches –
1.
2.
Sympathetic Nervous System
o Thoracic/lumbar (T1-L2/3)
o Prepare body for emergencies – fight or flight
o Short pre-ganglionic fiber, long post-ganglionic fiber, synapse in sympathetic trunk (along sides
of spinal cord) and again at effector organ
o Receive sensory input from external world, viscera, hypothalamus, reticular formation, limbic
system, pre-frontal cortex
o Pre-ganglionic NT is acetylcholine (cholinergic fiber), post-ganglionic NT is norepinephrine
(adrenergic fiber)
o Pre-ganglionic receptor is nicotinic cholinergic, post-ganglionic receptor is adrenergic (alpha 1, 2
or beta 1, 2, 3)
Parasympathetic Nervous System
o Cranial/sacral (C3/7/9/10, S2-4, 75% vagus nerve)
o Maintain vegetative function – rest and digest
o Long pre-ganglionic fiber, short post ganglionic fiber, synapse in terminal ganglia near effector
organ and again on cells of organ
o Receive same sensory input as sympathetic
o Pre-ganglionic and post-ganglionic NT is acetylcholine (cholinergic fiber)
o Pre-ganglionic receptor is nicotinic cholinergic, post ganglionic receptor is muscarinic (subtypes
M1-7)
Pre-ganglionic NT
Post-ganglionic NT
Sympathetic
Acetylcholine
Norepinephrine
Parasympathetic
Acetylcholine
Acetylcholine
*Nicotinic and Muscarinic receptors are for acetylcholine
Pre-ganglionic
Receptor
Nicotinic
Nicotinic
Post-ganglionic
Receptor
Adrenergic
Muscarinic
Some autonomic function cannot be explained by SNS/PNS – called non-adrenergic non-cholinergic
transmission (NANC), we now know this is due to nitrous oxide (NO) or nitrergic transmission
There is dual innervation by both systems except in the following cases –
1.
2.
Blood vessels – only sympathetic
o Includes arteries/veins, not capillaries
o Vessels to penis and clitoris are dual
o In brain and penis, PNS stimulation releases NO causing vasodilation (Viagra mimics)
Sweat glands – only sympathetic
3.
o Secrete acetylcholine, not norepinephrine
Salivary glands – both
o Activity is not antagonistic, both stimulate salivary secretion
Neurotransmitters
Acetylcholine
Choline acetyltransferase
Synthesis – cholinergic neuron/axon/axon terminal Choline + Acetyl CoA --------------------------> Acetylcholine + CoA
Storage – synaptic vesicles in axoplasm of pre-synaptic neuron
Release – when AP arrives, Ca2+ ions cause Ach to exocytose into synaptic cleft. It is released at 1.
2.
3.
4.
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6.
All pre-ganglionic synapses including adrenal medulla
Parasympathetic (muscarinic) post-ganglionic synapse
Sympathetic (adrenergic) post-ganglionic synapse of sweat glands (sudomotor)
Some skeletal muscle blood vessels
Efferent nerves at NM junction (nicotinic subtype receptor)
Cholinergic neurons in brain
Binding – binds to nicotinic (mimicked by nicotine) and muscarinic receptors, alters permeability of cell to Ca2+,
Na+, K+ EPSP
Nicotinic receptors found at –
1.
2.
3.
4.
5.
Pre-ganglionic sympathetic and parasympathetic nerves
Autonomic ganglia
NM junction
Adrenal medulla
Brain
Muscarinic receptors found at –
1.
2.
Post-ganglionic parasympathetic nerves
Brain
Signal transduction – binding of ACh to receptors causes activation of 2nd messengers (Cyclic Guanine
Monophosphate (c-GMP) and G-proteins) which open/close ion channels
Termination – hydrolysis of ACh by enzymes such as acetyl cholinesterase, reuptake
Cholinergic Disease
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2.
3.
Myasthenia gravis – immune-destruction of cholinergic receptors and decreased release of ACh resulting
in muscle weakness
o Treatment is neostigmine – inhibits AChE temporarily to available ACh can bind to receptors
Botulinum toxin – blocks the release of ACh from pre-synaptic cell resulting in neuromuscular blockade
and respiratory paralysis, Botox treats muscle spasm, dystonia, involuntary movement, wrinkles
Black Widow spider venom – surge of ACh resulting in prolonged/unrelenting muscle contraction
4.
5.
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7.
Curare – cholinergic antagonist and neuromuscular blocker drug
Organophosphate (cholinesterase inhibitor)– inhibit acetyl cholinesterase so that ACh cannot metabolize
o Called cholinomemetic – mimics action of ACh
o Treatment is pralidoxime – cholinesterase reactivator
Alpha-Bungarotoxin – binds irreversibly to ACh receptor as cholinomemetic resulting in respiratory
blockage and death, snake venom
Alzheimer’s dementia, Parkinson’s, Down Syndrome and memory loss all involve ACh defects
Norepinephrine
Synthesis – axoplasm of pre-synaptic neurons, axons, chromaffin cells of adrenal medulla
Tyrosine ------------------>L-DOPA------------------->Dopamine------------------->Norepinephrine--------------->Epinephrine
*Dopamine, Norepinephrine, Epinephrine are catecholamines (also released from adrenal medulla)
Adrenal medulla – neuro-endocrine organ that produces and releases above catecholamines, can turn
norepinephrine to epinephrine using PNMT
Storage – transported to synaptic vesicles of axoplasm by vesicular monoamine transporter (VMAT) to prevent
degradation by monoamine oxidase enzyme (MAO)
Release – when AP arrives, Ca2+ causes NE to exocytose into synaptic cleft. It is released at –
1.
2.
3.
Sympathetic (adrenergic) post-ganglionic synapse (except sweat gland/some skeletal blood vessels)
Adrenal medulla into blood (epinephrine > norepinephrine)
Large/diffuse areas of brain
Termination –
1.
2.
3.
Diffusion of NE from site of action
Uptake 1 – reuptake into axoplasm of pre-synaptic neuron, NE becomes inactivated by MAO to VMA or
COMT inactivates NE to normetanephrines
Uptake 2 – reuptake into non-neural tissue in vicinity
Adrenergic Drugs
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Sympathomimetic drug – mimics NE as agonist (salbutamol, albuterol)
Tyramine, Amphetamine – increase release of NE from pre-synaptic cell
Monoamine Oxidase Inhibitors – prevent breakdown of catecholamines by MAO enzymes, also called
tricyclic antidepressants (TCA)
Cocaine – blocks NE reuptake into pre-synaptic cell
Sympatholytic drug –
o Reserpine depletes NE from vesicle stores (hypertension)
o Guanathedine, Debrisoquine – prevent NE from exocytosis (adrenergic neuron blocker)
o Prazosin (alpha 1 blocker), Atenolol, Metoproadrenergic (Beta blocker) – bind to post-synaptic
membrane to block NE from binding
Adrenergic Diseases
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Autonomic failure w/ hypotension (Shy-Draggar/Riley-Day familial dysauntonomia) – BP falls when
sleeping or standing (alpha 1)
Pheochromocytoma – tumor of adrenals producing NE/E even w/ hyper/hypotension
ADHD – deficient production of NE and dopamine in brain
o Treated with Ritalin (methylphenidate) a psychostimulant
Depression – low levels of NE/serotonin in synapse, less stimulation in prefrontal cortex
Bipolar – abnormal metabolism and receptor population of adrenergic receptors
Diabetes mellitus, heart failure, obesity, chronic renal failure relate to autonomic neuropathy
Dopamine
Catecholamine transmitter that acts on dopamine receptors (DA) in the kidneys (renal arterial dilation and
natriuresis) and brain
1.
2.
3.
At low concentration  stimulates DA 1 and 2
At middle concentration  stimulates Beta 1 and 2
At high concentration  stimulates alpha 1 (vasoconstriction)
Receptors
Adrenergic
Receptor Type
2nd Messenger Effect
Alpha
2
Inositol Triphosphate
(IP3)
Increase Ca2+
Decrease cAMP
1
Increase cAMP
2
Increase cAMP
3
-
Beta
1
Organ/tissue
Distribution
Vascular smooth
muscle
Muscle of iris
Pre-synaptic neuron
Heart (80%)
Kidney
Brain
Eye
Heart (20%)
Blood vessels
Bronchus
Uterus
Liver
Eye
Adipose tissue
Stimulation Effect
Vasoconstriction
Pupil dilation (mydriasis)
Inhibits NE
Relax GIT smooth muscle
Increase contraction
Release rennin
Mood changes
Produce aqueous humor
Increase contraction
Vasodilation
Bronchodilation
Muscle relaxation
Glycogenolysis
Produce aqueous humor
Lipolysis
Affinity for
Catecholamines
NE>E
NE>E
NE=E
E>NE
E only