Influence of Nicorandil on Catecholamine Release in the Perfused Rat Adrenal Medulla

Influence of Nicorandil on Catecholamine Release in the Perfused Rat Adrenal Medulla

The present study was attempted to investigate the effect of nicorandil, which is an ATP-sensitive potassium (KATP) channel opener, on secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane depolarization from the isolated perfused rat adrenal glands. The perfusion of nicorandil (0.3∼3.0 mM) into an adrenal vein for 90 min produced relatively dose-and time-dependent inhibition in CA secretion evoked by ACh (5.32 mM), high K<SUP>+</SUP> (a direct membrane depolarizer, 56 mM), DMPP (a selective neuronal nicotinic receptor agonist, 100μM for 2 min), McN-A-343 (a selective muscarinic M1 receptor agonist, 100μM for 4 min), Bay-K-8644 (an activator of L-type dihydropyridine Ca<SUP>2&#8290;</SUP> channels, 10μM for 4 min) and cyclopiazonic acid (an activator of cytoplasmic Ca<SUP>2&#8290;</SUP>-ATPase, 10μM for 4 min). In adrenal glands simultaneously preloaded with nicorandil (1.0 mM) and glibenclamide (a nonspecific KATP-channel blocker, 1.0 mM), the CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were recovered to the considerable extent of the control release in comparison with that of nicorandil-treatment only. Taken together, the present study demonstrates that nicorandil inhibits the adrenal CA secretion in response to stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by membrane depolarization from the isolated perfused rat adrenal glands. It seems that this inhibitory effect of nicorandil may be mediated by inhibiting both Ca<SUP>2&#8290;</SUP> influx and the Ca<SUP>2&#8290;</SUP> release from intracellular store through activation of KATP channels in the rat adrenomedullary chromaffin cells. These results suggest that nico</SUP>randil-sensitive KATP channels may play an inhibitory role in the regulation of the rat adrenomedullary CA secretion.