Activation of dihydropyridine-sensitive calcium channels induces somatostatin release from hypothalamic neurons. Pharmacological characterization.
The current study was designed to determine whether dihydropyridine voltage-sensitive calcium channels were involved in the release of somatostatin from hypothalamic neurons, BAY K 8644 (?) a dihydropyridine with Ca(2+) channel agonistic properties elicited a dose-response release of somatostatin. The secretory responses observed either in the presence of 5 mM K(+) or 15 mM K(+) were similar; the EC(50) values were 9.6+/-0.05 nM and 9.3+/-0.08 nM respectively. Nifedipine, a dihydropyridine Ca(2+) channel antagonist and diltiazem, a benzothiazepine that also inhibits dihydropyridine sensitive Ca(2+) channels, decreased Bay K 8644-induced somatostatin release in a dose-dependent manner with IC(50)s of 0.39 +/- 0.05 ?M and 66+/-0.07 ?M. Verapamil, a phenylalkylamine tested at 50 ?M inhibited the evoked release by 65%. ?-conotoxin at concentrations ranging from 1 nM to 1 ?M, decreased BAY K 8644-stimulated somatostatin release in a dose-related manner, the lowest effective concentration being 1 nM. None of these drugs affected basal or K(+)-evoked release of somatostatin. These data suggest that in our experimental conditions, activation of dihydropyridine voltage sensitive-Ca(2+) channels induces somatostatin exocytosis although normally the Ca(2+) channels associated with stimulus-secretion coupling of somatostatin would not be dihydropyridine sensitive.
Tapia-Arancibia
L
L
Unité de Neurobiologie Endocrinologique, CNRS, UA 1197, Université de Montpellier II, 34095 Montpellier Cedex 5, France.
Humbert
T
T