Stimulation by melittin of adrenocorticotropin and beta-endorphin release from rat adenohypophysis in vitro.
The effect of melittin on the release of adrenocorticotropin (ACTH) and beta-endorphin from the corticotropic cells of the rat adenohypophysis was examined in vitro. Anterior pituitary quarters were perifused or incubated in vitro and ACTH- (ACTH-IR) or beta-endorphin-like immunoreactivity (beta-End-IR) in the medium was measured by radioimmunoassays. Melittin stimulated ACTH-IR and beta-End-IR release. This effect was rapid in onset, reversible, and concentration-related (50-5000 ng/ml) and depended on the presence of calcium ions in the incubation medium. Melittin also elevated the tissue content of unesterified 3H-arachidonic acid that had previously been incorporated into lipids. Purported phospholipase A2 inhibitors, mepacrine (up to 1 mM), dexamethasone (0.5 mg/kg in vivo, 50 nM in vitro), or p-bromophenacylbromide (100 microM), did not decrease the melittin (500 ng/ml) - induced beta-End-IR release, although mepacrine and dexamethasone may have inhibited phospholipase A2 activity as indicated by an inhibition of melittin-evoked prostaglandin E2 formation. After stimulation by melittin (500 ng/ml), beta-End-IR release was not affected by the cyclooxygenase inhibitor indomethacin (up to 140 microM), whereas nordihydroguaiaretic acid (100 microM), a lipoxygenase inhibitor, or BW755C (250 microM), an inhibitor of both cyclooxygenase and lipoxygenase, abolished melittin-induced hormone secretion. We conclude that melittin generates a signal in the corticotropic cells of the rat adenohypophysis which induces hormone secretion by exocytosis. This signal may be unrelated to the activation by melittin of phospholipase A2.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001514:Bee Venoms / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004723:Endorphins / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008555:Melitten / Q000494:pharmacology*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D001615:beta-Endorphin
D001514:Bee Venoms; D004723:Endorphins; D008555:Melitten; D001615:beta-Endorphin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine; D002118:Calcium