ANS Review

Elsevier’s Integrated Review Pharmacology , Second Edition
(also includes a figure from wiki, and Rang and Dale)

This was an Excellent Chapter…thoroughly enjoyed it!

Parasympathetic (acetylcholine [ ACh]) synthesis and degradation. ACh is synthesized from choline and acetyl–coenzyme A ( CoA), a reaction that is catalyzed by choline acetyltransferase. Once released into the synapse, ACh is degraded by acetylcholinesterase into choline (which gets recycled for reuse) and acetate. This process takes place in all the colored boxes.

Schematic diagrams of the parasympathetic (acetylcholine) receptors. A, Nicotinic receptors (N N or N M) are ligand-gated ion channels. After stimulation, the resulting depolarization in neurons (NN type) leads to a neuronal action potential, whereas depolarization in muscles (N M type) leads to muscular contraction. B, Acetylcholine muscarinic receptors are 7-transmembrane domain G-protein–coupled receptors (7 TM-GPCR) found at postganglionic terminals, representing the parasympathetic innervation of an end-organ. Note that the muscarinic receptor can be either stimulatory or inhibitory depending on the signal transduction mechanism to which it is coupled. As before (see Fig. 6-3) these two types of ACh receptors are in the colored compartments.

Muscarinic M1/M3/M5 acetylcholine receptors. The “odd” class of muscarinic receptors works through an α q G-protein to activate a membrane-associated phospholipase C. GTP, guanosine triphosphate; DAG, diacylglycerol; IP, inositol triphosphate.

Reciprocal regulation of adenylyl cyclase by muscarinic and adrenergic receptors. A, The M2/M4 “even” class of muscarinic receptors works through an α i-inhibitory G-protein to reduce synthesis of cyclic adenosine monophosphate ( cAMP). This inhibition results in reduced intracellular signaling. B, The β-adrenergic receptors work through an α s-stimulatory G-protein to activate adenylyl cyclase and increase the production of cAMP from adenosine triphosphate. These receptors frequently reside on the same organs to provide reciprocal regulation. PKA, protein kinase A; GTP, guanosine triphosphate.

Catecholamine biosynthesis. Adrenergic biosynthesis begins with an essential amino acid—tyrosine—and its hydroxylation by the rate-limiting enzyme tyrosine hydroxylase. This reaction produces a benzene ring with neighboring hydroxyl groups. This chemical is called catechol and is the reason this class of molecules (all of subsequent molecules in the pathway) is collectively referred to as the catecholamines.

Termination of adrenergic responses. A, Most sympathetic signaling is terminated through reuptake (and repackaging and reuse) via a norepinephrine transporter. B, Enzymatic degradation of the catecholamines, a minor mechanism for signal termination, is also involved in terminating norepinephrine actions. The empty brackets represent less important chemical intermediaries. As noted in Chapter 13, several treatments in the central nervous system (especially for Parkinson disease) target these degradation enzymes. COMT, catechol- O-methyltransferase; MAO, monoamine oxidase; MHPG, 3-methoxy-4-hydroxyphenylglycol; Tyr, tyrosine; VMA, vanillomandelic acid.

Rang and Dale:
Presynaptic regulation of transmitter release from noradrenergic and cholinergic nerve terminals.

Physiology and pharmacology of adrenergic receptors. cAMP, cyclic adenosine monophosphate; TPR, temperature; BP, blood pressure.

Reciprocal action by the α 1– and α 2-receptors. The α-receptors are 7-transmembrane-spanning domain, G-protein–coupled receptor proteins and are coupled to lipid metabolism or inhibition of cyclic adenosine monophosphate ( cAMP) synthesis. GTP, guanosine triphosphate; PIP 2 , phosphatidylinositol 4,5-bisphosphate; IP 3 , inositol triphosphate; DAG, diacylglycerol.

Stimulation of adenylyl cylcase by the β-receptors. All the β-receptors are coupled to a stimulatory G-protein ( s ) and increase synthesis of cyclic adenosine monophosphate ( cAMP). Stimulation of β-receptors produces widely different effects depending on downstream effectors present in specific cells. In this case, cAMP triggers dissociation of the inactive protein kinase A holoenzyme ( R 2 C 2) into regulatory subunit dimers ( R 2 •cAMP 4) and active catalytic subunits ( CGTP, guanosine triphosphate; ATP, adenosine triphosphate.


The mechanism of adrenergic receptors. Adrenaline or noradrenaline are receptor ligands to either α1α2 or β-adrenergic receptors. α1 couples to Gq, which results in increased intracellularCa2+ and subsequent smooth muscle contraction. α2, on the other hand, couples to Gi, which causes a decrease in neurotransmitter release, as well as a decrease of cAMP activity and a resulting and smooth muscle contraction. β receptors couple to Gs, and increases intracellular cAMP activity, resulting in e.g. heart muscle contraction, smooth muscle relaxation and glycogenolysis.

Pharmacologic profiles of adrenergic drugs. A, Adrenergic agonists. B, Adrenergic antagonists. Selectivity is indicated by the position of the drug on the α-to-β continuum.

Role of noninnervated β-receptors in the regulation of blood pressure. Peripheral blood vessels are innervated by sympathetic nerves that release norepinephrine and stimulate α 1-receptors. In addition, the vessels contain noninnervated β 2-receptors that normally respond to circulating epinephrine. The former receptors produce vasoconstriction (increased blood pressure), whereas the latter produce vasodilation (decreased blood pressure).

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