CALMODULIN INVOLVEMENT ON THE CA++-DEPENDENT RELEASE OF LHRH AND SRIF INVITRO

Mediobasal hypothalamic (MBH) slices of male adult rats were superfused at 37.degree. C with oxygenated Hepes-buffer Locke medium. Bacitracin (2 .times. 10-5 M) was added to prevent enzymatic degradation of LHRH and SRIF [somatototropine release-inhibiting factor]. A 6 min pulse of K+ (56 mM), veratridine (15 .mu.M) or the ionophore A23187 [calcimycin](10-5 M), markedly stimulated the release of both neuropeptides. Trifluoperazine, a calmodulin inhibitor, decreased the K+-evoked LHRH and SRIF release in a dose-dependent manner; it was also effective in inhibiting the veratridine-induced neuropeptides release. Phenytoin, a calmodulin-dependent kinase inhibitor, also decreased in a dose-dependent manner the K+-induced LHRH and SRIF release; the basal release of both neuropeptides remained unaffected by either treatment. The ionophore-stimulated release of both neuropeptides was significantly inhibited as well. A Ca2+-calmodulin kinase system may be involved in the mechanism of depolarization-induced LHRH and SRIF release from hypothalamic nerve terminals.