Effects of Ca channel antagonists on acetylcholine and catecholamine releases in the in vivo rat adrenal medulla

Akiyama, Tsuyoshi, Toji Yamazaki, Hidezo Mori, and Kenji Sunagawa. Effects of Ca channel antagonists on acetylcholine and catecholamine releases in the in vivo rat adrenal medulla. Am J Physiol Regul Integr Comp Physiol 287: R161–R166, 2004. First published March 18, 2004; 10.1152/ajpregu.00609.2003.—To elucidate the types of voltage-dependent Ca channels controlling ACh and catecholamine releases in the in vivo adrenal medulla, we implanted microdialysis probes in the left adrenal medulla of anesthetized rats and investigated the effects of Ca channel antagonists on ACh, norepinephrine, and epinephrine releases induced by nerve stimulation. The dialysis probes were perfused with Ringer solution containing a cholinesterase inhibitor, neostigmine. The left splanchnic nerves were electrically stimulated at 2 and 4 Hz before and after intravenous administration of Ca channel antagonists. -Conotoxin GVIA (an N-type Ca channel antagonist, 10 g/kg) inhibited ACh release at 2 and 4 Hz by 40%, norepinephrine release at 4 Hz by 50%, and epinephrine release at 2 and 4 Hz by 45%. A fivefold higher dose of -conotoxin GVIA (50 g/kg) did not further inhibit these releases. -Conotoxin MVIIC (a P/Q-type Ca channel antagonist, 50 g/kg) inhibited ACh and epinephrine releases at 4 Hz by 30%. Combined -conotoxin GVIA (50 g/kg) and MVIIC (250 g/kg) inhibited ACh release at 2 and 4 Hz by 70% and norepinephrine and epinephrine releases at 2 and 4 Hz by 80%. Nifedipine (an L-type Ca channel antagonist, 300 and 900 g/kg) did not change ACh release at 2 and 4 Hz; however, nifedipine (300 g/kg) inhibited epinephrine release at 4 Hz by 20%, and nifedipine (900 g/kg) inhibited norepinephrine and epinephrine releases at 4 Hz by 30%. In conclusion, both Nand P/Q-type Ca channels control ACh release on preganglionic splanchnic nerve endings while L-type Ca channels do not. L-type Ca channels are involved in norepinephrine and epinephrine releases on chromaffin cells.