von Spreckelsen S, Lollike K, Treiman M
Institute of Medical Physiology C, Panum Institute, University of Copenhagen, Denmark.
Brain Res. 1990 Apr 23;514(1):68-76. doi: 10.1016/0006-8993(90)90436-f.
In order to study the role of different types of voltage-sensitive Ca2+ channels (VSCC) in stimulus-secretion coupling in peptidergic neurons, effects of 4 major classes of pharmacological agents have been examined on evoked vasopressin release from isolated rat neurohypophyses. omega-Conotoxin GVIA (omega-CgTX), a potent blocker of N- and L-type Ca2+ channels, inhibited vasopressin release evoked electrically as well as by high K+. With maximal inhibition, release was decreased to 50% and 75% of control for electrical and 100 mM K+ stimulation, respectively. This stimulation mode-related difference in release sensitivity to omega-CgTX paralleled its stimulation mode-related sensitivity to tetrodotoxin, suggesting that the omega-CgTX-sensitive Ca2+ entry played a larger role when release was activated by action potentials invading nerve terminals. These data, and the characteristics of [125I]omega-CgTX binding to plasma membranes from bovine neurohypophyses, are consistent with N-type Ca2+ channels being responsible for the omega-CgTX-sensitive component of vasopressin release. Verapamil and diltiazem (phenylalkylamine and benzothiazepine, respectively) inhibited secretion in a pattern suggesting non-identical sets of action sites, and in a manner partly additive with inhibition by omega-CgTX. This inhibition by verapamil and diltiazem appeared at least in part to involve sites different from L channels. Several dihydropyridines known to act as agonists or antagonists at L channels did not affect vasopressin release (evoked either electrically or by high K+) in a specific manner. A significant component of neuropeptide release may depend on Ca2+ entry through omega-CgTX- and dihydropyridine-insensitive routes.
