In the study reported here we have reached two conclusions. First, the cat adrenal medulla chromaffin cell possesses a dopamine D1 receptor that seems to be coupled to an adenylyl cyclase. Second, this receptor regulates the muscarinic-mediated catecholamine release response through a negative feed-back loop which uses cyclic AMP as a second messenger. These conclusions are supported by the following findings: (i) SKF38393 (a selective D1 receptor agonist), but not quinpirole (a selective D2 agonist), inhibits the methacholine-mediated catecholamine release responses in a concentration-dependent manner (IC50 of around 1-2 microM). (ii) SCH23390 (a selective D1 antagonist), but not sulpiride (a selective D2 antagonist), reversed by 70% the inhibitory effects of SKF38393. (iii) Dibutyril cyclic AMP (500 microM) inhibited by 80% the secretory effects of methacholine.