The document describes the sympathetic nervous system and its neurotransmitters. It discusses how acetylcholine acts as the preganglionic neurotransmitter while norepinephrine, epinephrine, and dopamine act as postganglionic neurotransmitters. It also describes the effects of these neurotransmitters on adrenergic receptors, including their effects on cardiovascular function. Key drugs that act on the sympathetic nervous system are also mentioned.

1. INTRODUCTION: SYMPATHETIC AUTONOMIC PHARMACOLOGY I Philip J. Kadowitz, Ph.D.

9. Figure 6-1. Schematic diagram comparing some anatomic and neurotransmitter features of autonomic and somatic motor nerves. Only the primary transmitter substances are shown. Parasympathetic ganglia are not shown because most are in or near the wall of the organ innervated. Note that some sympathetic postganglionic fibers release acetylcholine or dopamine rather than norepinephrine. The adrenal medulla, a modified sympathetic ganglion, receives sympathetic preganglionic fibers and releases epinephrine and norepinephrine into the blood. (ACh, acetylcholine; D, dopamine; Epi, epinephrine; NE, norepinephrine; N, nicotinic receptors; M, muscarinic receptors.)

10. Figure 10–2. Effects of Intravenous Infusion of Norepinephrine, Epinephrine, or Isoproterenol in Human Beings. (Modified from Allwood Et Al., 1963 , with Permission.)

11. Figure 6-3. Schematic illustration of a generalized cholinergic junction (not to scale). Choline is transported into the presynaptic nerve terminal by a sodium-dependent carrier (A). This transport can be inhibited by hemicholinium drugs. ACh is transported into the storage vesicle by a second carrier (B) that can be inhibited by vesamicol. Peptides (P), ATP, and proteoglycan are also stored in the vesicle. Release of transmitter occurs when voltage-sensitive calcium channels in the terminal membrane are opened, allowing an influx of calcium. The resulting increase in intracellular calcium causes fusion of vesicles with the surface membrane and exocytotic expulsion of ACh and cotransmitters into the junctional cleft. This step is blocked by botulinum toxin. Acetylcholine's action is terminated by metabolism by the enzyme acetylcholinesterase. Receptors on the presynaptic nerve ending regulate trans-mitter release. (SNAPs, synaptosome-associated proteins; VAMPs, vesicle-associated membrane proteins.)

12. The enzymes involved are shown in blue; essential cofactors, in italics. The final step occurs only in the adrenal medulla and in a few epinephrine-containing neuronal pathways in the brainstem.

13. Figure 6-6. Metabolism of catecholamines by catechol- O- methyltransferase ( COMT ) and monoamine oxidase (MAO). (Modified and reproduced, with permission, from Greenspan FS, Gardner DG (editors): Basic and Clinical Endocrinology, 7th ed. McGraw-Hill, 2003.)