Influence of quinine on catecholamine release evoked by cholinergic stimulation and membrane depolarization from the rat adrenal gland.

The present study was attempted to investigate the effect of quinine on secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane depolarization from the isolated perfused rat adrenal gland. The perfusion of quinine (15-150 microM) into an adrenal vein for 60 min produced dose- and time-dependent inhibition in CA secretion evoked by ACh (5.32 x 10(-3) M), high K+ (5.6 x 10(-2) M), DMPP (10(-4) M for 2 min), McN-A-343 (10(-4) M for 2 min), cyclopiazonic acid (10(-5) M for 4 min) and Bay-K-8644 (10(-5) M for 4 min). Also, under the presence of pinacidil (10(-4) M), which is also known to be a selective potassium channel activator, CA secretory responses evoked by ACh, high potassium, DMPPF McN-A-343, Bay-K-8644 and cyclopiazonic acid were also greatly reduced. When preloaded along with quinine (5 x 10(-5) M) and glibenclamide (10(-6) M), a specific blocker of ATP-regulated potassium channels, CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were recovered as compared to those of quinine-treatment only. Taken together, these results demonstrate that quinine inhibits CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by membrane depolarization through inhibiting influx of extracellular calcium and release in intracellular calcium in the rat adrenomedullary chromaffin cells. These findings suggest that activation of potassium channels may be involved at least in inhibitory action of quinine on CA secretion from the rat adrenal gland.