(embryologically, the medulla is a modified ganglion and therefore uses ACh as a
transmitter). This allows the inflow of Ca^2 +, which triggers fusion of the chromaffin cell
membrane with the secretory vesicle, resulting in exocytosis of the entire vesicle con-
tents including all of the vesicle proteins. The release and turnover of catecholamines
is subject to complex regulation, the most important type of which is modulation by
presynaptic receptors. Adrenergic agonists acting on these receptors will decrease—
whereas antagonists will increase—neurotransmitter release, and also seem to have an
effect on regulating neurotransmitter synthesis. In addition, prostaglandins of the E
(PGE) series are potent inhibitors of neural NE release through a feedback loop involv-
ing Ca^2 +ions. These presynaptic receptors also respond to neuropeptide Y (NPY)
(section 4.10.2), enkephalin (chapter 5), dopamine (section 4.4), muscarinic agonists,
and angiotensin (chapter 5), in addition to adrenergic αandβagonists (section 4.3.6).
Acetylcholine and cAMP also seem to regulate catecholamine release. These presy-
naptic heteroreceptors are more likely to have a regulatory role in adrenergic synapses
than are the autoreceptors.
4.3.2.4 Catecholamine Metabolism and Reuptake
The metabolism of catecholamines is much slower and more complex than that of ACh.
The degradative pathways are shown in figure 4.7. The principal, although nonspecific,
enzyme in the degradation is monoamine oxidase (MAO), which dehydrogenates
220 MEDICINAL CHEMISTRY
Figure 4.6 Biosynthesis of catecholamines.