Physiology of the Autonomic Nervous System

Anatomy and Physiology

L|E|C|O|M Mathew J. Bateman, Ph.D., D.H.Ed.

Definitions

Agonist – a chemical substance capable of activating a

receptor to induce a full or partial pharmacological response.

Antagonist – a drug that counteracts the effects of another

drug.

Somatic vs. Autonomic

Receptors

Nicotinic Cholinergic Receptors

First efferent receptor outside CNS– Acetylcholine is the pre-synaptic neurotransmitter

– NM (Nicotinic-Muscle) receptor for skeletal muscle

• “Neuromuscular blockers” block the NM receptor

– NN (Nicotinic-Nerve) receptor for ganglia

• “Ganglionic blockers” block the NN receptor

Receptor activation opens sodium channels– Generates action potential in postsynaptic muscle– Generates EPSP in postsynaptic neurons

Nicotinic Synapse

Parasympathetic

Muscarinic ReceptorsReceptors for post-ganglionic receptors

– All parasympathetic – Few sympathetic

Five major subclasses, M1 thru M5M1, M4 and M5 are mostly in CNSThe heart is mostly M2

• M2 is an inhibitory receptor• Acts by reducing cyclic AMP

Most glands & smooth muscle have M3• M3 is an excitatory receptor• Acts by increasing calcium

Other types of receptors may be present

Muscarinic Synapse

Ach

AchReceptor

Choline + Acetate

Post synapticHeart (M2 receptor)OrGland/Smooth Muscle(M3)

Reuptake

Ach

+

AchEsterase

AchE Inhibitors

Muscarinic Blockers

G Protein

Muscarine & otherAgonists

cyclic AMP (M2)

Calcium (M3)

Diet

Parasympathetic Drugs

Parasympatholytics Suppress parasympathetic activity

Antagonists, specific to general• ganglionic, neuromuscular (nicotinic cholinergic)• M1 thru M5 (muscarinic cholinergic)

ParasympathomimeticsEnhance parasympathathetic activity

Cholinesterase inhibitors

Agonists• Specificity, as with antagonists

Sympathetic Receptors

Sympathetics

Cholinergic synapse at ganglia:• Acetylcholine (ACh) is neurotransmitter• Nicotinic cholinergic receptors on postganglionic cell

body membrane

Adrenergic synapse at target organ:• Norepinephrine (NE; noradrenalin) is

neurotransmitter • Acetylcholine (sympathetic [muscarinic] cholinergic)

receptors on sweat gland cells.

Adrenergic ReceptorsNorepinephrine binds to 2 classes of receptors

– alpha adrenergic receptors• Typically excitatory

– beta adrenergic receptors• Typically inhibitory

Sympathetic Adrenergic Receptors: receptors & receptors

Function by means of 2nd messengers– α1 increases calcium– α2 reduces cyclic AMP– β receptors increase cyclic AMP

Adrenergic Synapse

N.E.

N.E,Receptor

Post synaptic 1, 2 (smooth muscle)1 (Heart) 2 (smooth muscle)or 3 (adipocytes)

Reuptake

+

G Protein

L-DOPA

Dopamine

N.E.

N.E.

cyclic AMP ()

cyclic AMP (2)

Calcium (1)

COMT & MAO

Homovanillic Acid (HVA)

uptake

Urine

N.E.Adrenergic Blockers

AdrenergicAgonists

MAO or COMT Inhibitors

Reserpine

Adrenergic Receptors

Alpha Receptors– Norepinephrine has high affinity for alpha receptors– Epinephrine has lower affinity for alpha receptors

Alpha 1 receptors increase calcium – This is usually stimulatory – sub-subclasses: 1A 1B 1C

Alpha 2 receptors reduce cyclic AMP – This may be stimulatory or inhibitory, depending on the cell

type– sub-subclasses: 2A 2B 2C

Adrenergic Receptors

Beta Receptors– Epinephrine & N.E. have high affinity for beta receptors– Beta receptors increase cyclic AMP

This may be stimulatory or inhibitory, depending on the cell type

Adrenal Medulla

• Chromaffin cells of adrenal medulla act like “postganglionic sympathetics”.

• Have nicotinic cholinergic receptors on cell bodies

• Release catecholamines: epinephrine (~80%), norepinephrine (~20%), dopamine (trace)

• Systemic effects: similar to activation of the sympathetic nervous system.

“Fight or Flight”Sympathetic Defense Response

• Increased arterial pressure• Increased heart rate and contractility• Increased blood flow to skeletal muscles• Decreased blood flow to GI tract• Increased cellular metabolism• Increased glycogenolysis and blood glucose• Increased pupil diameter/lens flattening

Parasympathetic Response (DEM B2LUES3)

Defecation

Emesis (vomiting)

Miosis

Bradycardia, Bronchoconstriction

Lacrimation (tearing)

Urination

Erection

Salivation, Secretions, Sweating

(normally a sympathetic response)

Dual Innervation