Inhibitory mechanism of bromocriptine on catecholamine release evoked by cholinergic stimulation and membrane depolarization from the rat adrenal medulla.

The purpose of this study was to determine whether bromocriptine affects the catecholamines (CA) secretion evoked in isolated perfused rat adrenal glands, by cholinergic stimulation, membrane depolarization and calcium mobilization, and to establish the mechanism of its action. The perfusion of bromocriptine (1-10 microM) into an adrenal vein, for 60 min, produced relatively dose-dependent inhibition in the secretion of catecholamines (CA) evoked by acetylcholine (ACh, 5.32 mM), DMPP (100 microM for 2 min), McN-A-343 (100 microM for 2 min), cyclopiazonic acid (CPA, 10 microM for 4 min) and Bay-K-8644 (10 microM for 4 min). High K+ (56 mM)-evoked CA release was also inhibited, although not in a dose-dependent fashion. Also, in the presence of apomorphine (100 microM), which is also known to be a selective D2-agonist, the CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were also significantly depressed. However, in adrenal glands preloaded with bromocriptine (3 microM) in the presence of metoclopramide (15 microM), a selective D2-antagonist, the CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid considerably recovered as compared to that of bromocriptine only. Taken together, these results suggest that bromocriptine can inhibit the CA secretion evoked by stimulation of cholinergic receptors, as well as by membrane depolarization, in the perfused rat adrenal medulla. It is thought this inhibitory effect of bromocriptine may be mediated by inhibiting the influx of extracellular calcium and the release from intracellular calcium stores, through the activation of dopaminergic D2-receptors located in the rat adrenomedullary chromaffin cells. Furthermore, these findings also suggest that the dopaminergic D2-receptors may play an important role in regulating adrenomedullary CA secretion.