CNS Pre-ganglionic Ganglion Post-ganglionic Effectors Ach Ach lelueJo Parasympathetic Cardiac smooth muscles,gland cells, Nicotinic Muscarinic nerve terminals Sympathetic Ach NE Cardiac smooth muscles,gland cells, Nicotinic Adrenergic nerve terminals (a,) Sympathetic Ach Ach Sweat glands Nicotinic Muscarinic Sympathetic Ach D Renal vascular smooth muscle Nicotinic Dopaminergic (D1) Ach Sympathetic (adrenal medulla) Epi Released into blood Nicotinic Ach leJoes Motor (somatic) Skeletal muscle Nicotinic Ach acetylcholine D=dopamine Epi epinephrine NE norepinephrine
Thoracolumbar Cranial Sacral CNS Pre-ganglionic Ganglion Post-ganglionic Parasympathetic Ach Nicotinic Ach Nicotinic Ach Nicotinic Ach Nicotinic Ach Nicotinic Epi Sympathetic Sympathetic Sympathetic Sympathetic (adrenal medulla) Motor (somatic) Ach Ach Muscarinic Muscarinic NE Adrenergic () D Dopaminergic (D1) Ach Nicotinic Cardiac & smooth muscles, gland cells, nerve terminals Cardiac & smooth muscles, gland cells, nerve terminals Sweat glands Renal vascular smooth muscle Released into blood Skeletal muscle Ach = acetylcholine D = dopamine Epi = epinephrine NE = norepinephrine Effectors
Pharmacological division of cholinergic vs.adrenergic neurotransmission All preganglionic and parasympathetic postganglionic neurons use acetylcholine as neurotransmitter.Ach is the neurotransmitter at ganglia, nmj,and muscarinic tissue synapses. Most postganglionic sympathetic neurons use norepinephrine which is an adrenergic neurotransmitter. There are exceptions:Cholinergic transmission in sympathetic system all ganglia,adrenal medulla,sweat glads(muscarinic).Dopaminergic innervation in sympathetic system-renal blood vessels
• All preganglionic and parasympathetic postganglionic neurons use acetylcholine as neurotransmitter. Ach is the neurotransmitter at ganglia, nmj, and muscarinic tissue synapses. • Most postganglionic sympathetic neurons use norepinephrine which is an adrenergic neurotransmitter. Pharmacological division of cholinergic vs. adrenergic neurotransmission • There are exceptions: Cholinergic transmission in sympathetic system – all ganglia, adrenal medulla, sweat glads (muscarinic). Dopaminergic innervation in sympathetic system – renal blood vessels
Key Steps in Neurotransmission: Synthesis Storage Metabolism Action Release potential Recognition (action) Strategies for Pharmacological Intervention: Block synthesis and storage: Usually rate-limiting steps;produce long-term effects Block release: Rapid action and effective Interfere with metabolism: Can be reversible or irreversible;blocking metabolism increases effective neurotransmitter concentrations Interfere with action: Receptor antagonists agonists;high specificity
Synthesis & Storage Action potential Metabolism Recognition (action) Key Steps in Neurotransmission: Strategies for Pharmacological Intervention: Block synthesis and storage: Usually rate-limiting steps; produce long-term effects Block release: Rapid action and effective Interfere with metabolism: Can be reversible or irreversible; blocking metabolism increases effective neurotransmitter concentrations Interfere with action: Receptor antagonists & agonists; high specificity Release
Synthesis of acetylcholine: Choline Acetylcholine CH3、 CH3、 CH3-N+-CH2-CH2-OH Choline CHs-N*-CHz-CHz-O-C-CHs CH3 acetyltransferase + CH3+ 9 CoA-SH CoA-S-C-CH3 Acetyl-CoA CoA
Synthesis of acetylcholine: CH3 CH3 CH3 N+–CH2–CH2–OH CoA–S–C–CH3 O Choline Acetyl-CoA + Choline acetyltransferase CH3 CH3 CH3 N+–CH2–CH2–O–C–CH3 O CoA-SH + CoA Acetylcholine
Synthesis,storage and release of acetylcholine: Na* Choline (10HM Choline Synaptic ChAT cleft Ac-CoA Antiporter Ach Ach Nerve Ach choline impulse Ach acetic acid Ach Pre-synaptic N Ca2+ cell Ach AchE Ca2 Recognition by receptors NM CAT choline acetyltransferase AchE Post-synaptic AchE acetylcholinesterase cell
Synthesis, storage and release of acetylcholine: Pre-synaptic cell Post-synaptic cell Ach Ca2+ Na+ Choline (10 M) Choline Recognition by receptors Ca2+ Ach Ach Ach Nerve impulse NN NM Ach Ac-CoA ChAT Ach AchE AchE choline + acetic acid CAT = choline acetyltransferase AchE = acetylcholinesterase Synaptic cleft Antiporter