MASTOPARAN, A WASP VENOM PEPTIDE, STIMULATES RELEASE OF PROLACTIN FROM CULTURED RAT ANTERIOR-PITUITARY-CELLS

Studies have shown that mastoparan and other amphiphilic peptides indu ce exocytosis of hormones from anterior pituitary cells. We have studi ed the effect of mastoparan on the secretion of prolactin from culture d rat anterior pituitary cells and on the concomitant functional statu s of signal-transducing pathways in lactotroph-enriched cell. cultures . Mastoparan stimulation of prolactin secretion was dose-dependent, ti me-dependent, reversible and required the presence of calcium. Pretrea tment of pituitary cell cultures with cholera and pertussis toxin had no effect on the secretory response, whereas encapsulation of guanosin e 5-[beta-thio]diphosphate (GDP-beta-S) by reversible electropermeabil ization inhibited mastoparan-stimulated [H-3]inositol-labelled lactotr oph-enriched anterior pituitary cell cultures resulted in increased fo rmation of inositol phosphates compared with control cells, and encaps ulation of GDP-B-S blocked mastoparan-induced inositol lipid hydrolysi s. Mastoparan caused translocation of protein kinase C activity from a soluble to a membrane-attached form. Mastoparan was able to increase the intracellular Ca2+ concentration in Fura-2-loaded individual lacto trophs. Omission of Ca2+ from the extracellular medium did not change the Ca2+ response in lactotrophs when stimulated with mastoparan. On t he basis of these results it is concluded that mastoparan-induced rele ase of prolactin is preceded by activation of the inositol(1,4,5)trisp hosyhate/diacylglycerol pathway with resulting translocation of proter in kinase activity and increment in intracellular Ca2+. However, other signal-transducing pathways may be involved in the secretoly process.