A&p 17 receptors and signaling of the ans
Transcript of A&p 17 receptors and signaling of the ans
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