Abstract

Cat adrenal glands were perfused in situ with Locke's solution to compare the effects of certain local anesthetics (LA's) on medullary catecholamine release in response to acetylcholine (ACh) in normal Locke's solution or to calcium in the presence of 56 mM KCl. The ability of phenacaine and benzocaine to inhibit secretion elicited by ACh was somewhat less than their ability to depress secretion evoked by calcium alone. By contrast, benoxinate, a procaine analog, was better able to block release evoked by ACh than by calcium alone. In the presence of atropine and hexamethonium, dimethylprocaine, a potent stimulant of adrenomedullary secretion, exhibited a block of calcium-evoked release which was almost identical to that of procaine. These results lend further support to the hypothesis that certain LA's, because of their structural resemblance to ACh, inhibit medullary catecholamine release by a) interfering with the response to ACh by an action on or near ACh-sensitive sites and b) blocking the influx of calcium which follows chromaffin cell stimulation by ACh or excess K⁺. Other LA's which do not have the free tertiary amino group, such as phenacaine and benzocaine, produce their inhibitory activity solely by their action on calcium flux.