Studies have shown that
mastoparan and other amphiphilic
peptides induce exocytosis of
hormones from anterior pituitary cells. We have studied the effect of
mastoparan on the secretion of
prolactin from cultured rat anterior pituitary cells and on the concomitant functional status of signal-transducing pathways in lactotroph-enriched cell cultures.
Mastoparan stimulation of
prolactin secretion was dose-dependent, time-dependent, reversible and required the presence of
calcium. Pretreatment of pituitary cell cultures with
cholera and
pertussis toxin had no effect on the secretory response, whereas encapsulation of
guanosine 5-[beta-thio]
diphosphate (
GDP-beta-S) by reversible electropermeabilization inhibited
mastoparan-stimulated secretion. Incubation of
mastoparan with myo-[3H]
inositol-labelled lactotroph-enriched anterior pituitary cell cultures resulted in increased formation of
inositol phosphates compared with control cells, and encapsulation of
GDP-beta-S blocked
mastoparan-induced
inositol lipid hydrolysis.
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 lactotrophs. Omission of Ca2+ from the extracellular medium did not change the Ca2+ response in lactotrophs when stimulated with
mastoparan. On the basis of these results it is concluded that
mastoparan-induced release of
prolactin is preceded by activation of the
inositol(1,4,5)trisphosphate/
diacylglycerol pathway with resulting translocation of
protein kinase activity and increment in intracellular Ca2+. However, other signal-transducing pathways may be involved in the secretory process.