Postganglionic synapses

Mechanism of Action An antihypertensive that produces long-lasting noncompetitive alpha-adrenergic blockade of postganglionic synapses in exocrine glands and smooth muscles. Relaxes urethra and increases opening of the bladder. Therapeutic Effect Controls hypertension. 

Acetylcholine (ACh) has been known as a neurotransmitter since the mid-1920s. In fact, the demonstration that acetylcholine is the Vagusstoff ( vagus-substance ) released from the vagus nerve to modulate heart function was the first proof for the chemical mediation of nerve impulses (Loewi and Navratil, 1926). In the peripheral nervous system, ACh is found as the neurotransmitter in the autonomic ganglia, the parasympathetic postganglionic synapse, and the neuromuscular endplate. 

Norepinephrine (NE), a catecholamine, was first identified as a neurotransmitter in 1946. In the peripheral nervous system, it is found as the neurotransmitter in the sympathetic postganglionic synapse. 

As indicated in Figure 18-1, the transmitter at the preganglionic-postganglionic synapse in both divisions is acetylcholine, as is the transmitter at the parasympathetic postganglionic-effector cell synapse. The transmitter at the sympathetic postganglionic-effector cell synapse is usually norepinephrine. A small number of sympathetic postganglionic fibers, however, also use acetylcholine as their neurotransmitter. 

Norepinephrine (NE), a catecholamine, was first identified as a neurotransmitter in 1946. In the peripheral nervous system, it is found as a neuro transmitter in the sympathetic postganglionic synapse. NE is synthesized by the enzyme dopamine-p-hydroxylase (DbH) from the precursor dopamine (which is derived from tyrosine via DOPA). The rate-limiting step is the production of DOPA by tyrosine hydroxylase, which can be activated through phosphorylation. NE is removed from the synapse by two mechanisms (1) catechol-O-methyl-transferase (COMT), which degrades intrasynaptic NE, and (2) the norepinephrine transporter (NET), the primary way of removing NE from the synapse. Once internalized, NE can be degraded by the intracellular enzyme monoamine oxidase (MAO). 

The term antimuscarinic is derived from the action of acetylcholine at the postganglionic synapse which is closely imitated by the alkaloid, muscarine. 

Although the specificity of receptors is not so strict as that of the most important anabolic and catabolic enzymes, it is at least as strict as the degrad-ative enzymes of microsomes (see Section 3.5). Thus at ganglia, nicotine (but not muscarine) can take the place of acetylcholine, whereas at postganglionic parasympathetic synapses, muscarine (but not nicotine) can take its place (see Table 7.1). Further specificity is shown in acetylcholine antagonism, for which tubocurarine is specific at the neuromuscular junction, hexamethonium at ganglia, and atropine at parasympathetic postganglionic synapses. 

Most of what we know of the structure of the muscarinic receptor has been gleaned from studies of structure-activity relationships among agonists that mimic acetylcholine at the postganglionic synapses. These are the receptors traditionally termed muscarinic, but it must be kept in mind that this is a name of historical origin. Muscarine has no use in human medicine. Not much attention can be given to information derived from antagonists because these... 

---