Acetylcholine postganglionic neurons

Figure 9.2 Autonomic nerve pathways. All preganglionic neurons release acetylcholine (Ach), which binds to nicotinic receptors (N) on the postganglionic neurons. All postganglionic neurons in the parasympathetic system and some sympathetic postganglionic neurons innervating sweat glands release Ach that binds to muscarinic (M) receptors on the cells of the effector tissue. The remaining postganglionic neurons of the sympathetic system release norepinephrine (NE), which binds to alpha (a) or beta (P) receptors on cells of the effector tissue. The cells of the adrenal medulla, which are modified postganglionic neurons in the sympathetic system, release epinephrine (EPI) and NE into the circulation.

The action of administered acetylcholine on effector systems innervated by parasympathetic postganglionic neurons (smooth muscle cells, cardiac muscle cells, and exocrine gland cells) resembled the actions produced by the naturally occurring plant alkaloid muscarine. The actions of both acetylcholine and muscarine on the visceral effectors are similar to those produced by parasympathetic nerve stimulation. Furthermore, the effects of acetylcholine, muscarine, and parasympathetic nerve stimulation on visceral effectors are antagonized by atropine, another plant alkaloid. 

Ganglion blockers competitively block nicotinic cholinoceptors on postganglionic neurons in both sympathetic and parasympathetic ganglia. In addition, these drugs may directly block the nicotinic acetylcholine channel, in the same fashion as neuromuscular nicotinic blockers (see Figure 27-6). 

Consequently, all preganglionic neurons and parasympathetic postganglionic neurons are said to be cholinergic in nature because of the presence of acetylcholine at their respective synapses. Most sympathetic... 

FIGURE 18-1 Autonomic neurotransmitters and receptors. Preganglionic neurons (solid lines] release acetylcholine [ACh], Postganglionic neurons [dashed lines] release ACh in the parasympathetic pathways and norepinephrine [NE] in the sympathetic pathways. 

Adrenergic neurons (Figure 6-4) also transport a precursor molecule into the nerve ending, then synthesize the catecholamine transmitter, and finally store it in membrane-bound vesicles, but—as indicated in Figure 6-5—the synthesis of the catecholamine transmitters is more complex than that of acetylcholine. In most sympathetic postganglionic neurons, norepinephrine is the final product. In the adrenal medulla and certain areas of the brain, norepinephrine is further converted to epinephrine. Conversely, synthesis terminates with dopamine in the dopaminergic neurons of the central nervous system. Several important processes in these nerve terminals are potential sites of... 

Anticholinesterase insecticides phosphorylate the active site of cholinesterase in all parts of the body. Inhibition of this enzyme leads to accumulation of acetylcholine at affected receptors and results in widespread toxicity. Acetylcholine is the neurohormone responsible for physiologic transmission of nerve impulses from preganglionic and postganglionic neurons of the cholinergic (parasympathetic) nervous system, preganglionic adrenergic (sympathetic) neurons, the neuromuscular junction in skeletal muscles, and multiple nerve endings in the central nervous system (Fig. 10-5). 

Cholinergic transmission Acetylcholine (ACh) is the primary transmitter in all autonomic ganglia and at the parasympathetic postganglionic neuron-effector cell synapses. 

Ganglionic transmission Acetylcholine transmits both sympathetic and parasympathetic impulses from the "preganglionic" neurons in the brain and spinal cord to nicotinic ganglionic (N ) receptors on "postganglionic" neurons of the autonomic nervous system. This occurs in sympathetic ganglia, which are located along the spinal cord, and in parasympa-... 

The two most common neurotransmitters released by neurons of the ANS are acetylcholine (Ach) and norepinephrine (NE). Several distinguishing features of these neurotransmitters are summarized in Table 9.3. Nerve fibers that release acetylcholine are referred to as cholinergic fibers and include all preganglionic fibers of the ANS — sympathetic and parasympathetic systems all postganglionic fibers of the parasympathetic system and sympathetic postganglionic... 

The basis for the antihypertensive activity of the ganglionic blockers lies in their ability to block transmission through autonomic ganglia (Fig. 20.2C). This action, which results in a decrease in the number of impulses passing down the postganglionic sympathetic (and parasympathetic) nerves, decreases vascular tone, cardiac output, and blood pressure. These drugs prevent the interaction of acetylcholine (the transmitter of the preganglionic autonomic nerves) with the nicotinic receptors on postsynaptic neuronal membranes of both the sympathetic and parasympathetic nervous systems. 

As do most neuronal systems, cholinergic receptors show multiplicity, and we distinguish between nicotinic and muscarinic receptors, which differ in many respects. Whereas acetylcholine (4.1) binds to both types of receptors, the plant alkaloids nicotine (4.2) and muscarine (4.3) trigger a response only from nicotinic or muscarinic cholinergic receptors, respectively. Nicotinic receptors are found in all autonomic ganglia (i.e., in the sympathetic system as well as the parasympathetic) and at the neuromuscular endplate of striated muscle. Muscarinic receptors occur at postganglionic... 

Acetylcholine (ACh) The primary transmitter at ANS ganglia, at the somatic neuromuscular junction, and at parasympathetic postganglionic nerve endings. A primary excitatory transmitter to smooth muscle and secretory cells in the ENS. Probably also the major neuron-to-neuron ("ganglionic") transmitter in the ENS. 

The direct slowing of sinoatrial rate and atrioventricular conduction that is produced by muscarinic agonists is often opposed by reflex sympathetic discharge, elicited by the decrease in blood pressure (see Figure 6-7). The resultant sympathetic-parasympathetic interaction is complex because muscarinic modulation of sympathetic influences occurs by inhibition of norepinephrine release and by postjunctional cellular effects. Muscarinic receptors that are present on postganglionic parasympathetic nerve terminals allow neurally released acetylcholine to inhibit its own secretion. The neuronal muscarinic receptors need not be the same subtype as found on effector cells. Therefore, the net effect on heart rate depends on local concentrations of the agonist in the heart and in the vessels and on the level of reflex responsiveness. 

Autonomic nerves can regulate coronary arteriolar tone. Acetylcholine released from postganglionic parasympathetic nerves relaxes coronary arteriolar smooth muscle via the NO/cGMP pathway in humans as described above. Damage to the endothelium, as occurs with atherosclerosis, eliminates this action, and acetylcholine is able to contract arterial smooth muscle and produce vasoconstriction. Skeletal muscle receives sympathetic cholinergic vasodilator nerves, but the view that acetylcholine caused vasodilation in this vascular bed has not been verified experimentally. Moreover, NO, rather than acetylcholine, may be released from neurons. However, this vascular bed responds to exogenous choline esters because of the presence of M3 receptors on endothelial and smooth muscle cells. 

Historically, drugs that block activation of postganglionic autonomic neurons by acetylcholine were among the first agents used in the treatment of hypertension. Most such drugs are no longer available clinically because of intolerable toxicities related to their primary action (see below). 

The parasympathetic system is exclusively a cholinergic system. The neurotransmitter acetylcholine is produced at both pre- and post-ganglionic nerve cells. Acetylcholine is the neurotransmitter at the preganglionic neurons of the sympathetic system also, but the postganglionic sympathetic stimulation is by norepinephrine. 

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