title: Maitotoxin, a calcium channel activator, increases prolactin release from rat pituitary tumor 7315a cells by a mechanism that may involve leukotriene production.
abstract: Arachidonate and its metabolites may play an important role in the release of prolactin. In the present study, the effect of maitotoxin, a calcium channel activator, was measured on the release of arachidonate and its metabolites from the prolactin-secreting 7315a tumor. Maitotoxin increased the release of prolactin, arachidonate, prostaglandins E2 and F2 alpha (PGE2, PGF2 alpha) and leukotriene C4 (LTC4) from 7315a cells prelabeled with [3H]arachidonate. The magnitude of the increase of prolactin and arachidonate release was decreased in low-calcium medium. The release of arachidonate from cellular phospholipids is necessary for the effect of maitotoxin on prolactin release because quinacrine, an inhibitor of arachidonate hydrolysis from phospholipids, blocked the maitotoxin-induced release of prolactin. The ability of maitotoxin to induce prolactin release appears to require metabolic transformation of arachidonate to its metabolites because BW755c, an inhibitor of the conversion of arachidonate, blocked the maitotoxin-induced prolactin release. In particular, LTC4 may be an important component of the prolactin release process because nordihydroguaiaretic acid and nafazatrom, which block the production of leukotrienes and other lipoxygenase-generated products, decreased LTC4 and prolactin release without affecting arachidonate, PGE2 or PGF2 alpha production. In contrast, indomethacin, a prostaglandin synthesis inhibitor, decreased PGE2 and PGF2 alpha production without affecting LTC4 or prolactin release. These data indicate that release of LTC4 and prolactin are closely linked events in 7315a tumor cells.
mesh_terms: D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D007213:Indomethacin / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism; D008387:Marine Toxins / Q000494:pharmacology*; D035964:Oxocins; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D047069:Pyrazolones; D051381:Rats; D013189:SRS-A / Q000096:biosynthesis* / Q000378:metabolism; D000095702:Polyether Toxins
chemical_list: D016718:Arachidonic Acid; D001095:Arachidonic Acids; D002118:Calcium; D007213:Indomethacin; D007473:Ion Channels; D008387:Marine Toxins; D035964:Oxocins; D011388:Prolactin; D011453:Prostaglandins; D011720:Pyrazoles; D047069:Pyrazolones; D013189:SRS-A; C020394:maitotoxin; D000095702:Polyether Toxins; C018845:nafazatrom