title: Effect of various blockers of arachidonic acid metabolism on release of beta-endorphin- and adrenocorticotropin-like immunoreactivity induced by phospholipase A2 from rat adenohypophysis in vitro.
abstract: Anterior pituitary quarters were incubated in vitro and the release of beta-endorphin-like (beta-End-IR) and adrenocorticotropin-like immunoreactivity (ACTH-IR) was determined. The effect of phospholipase A2 as well as the effect of various compounds known to influence arachidonic acid metabolism under certain conditions were examined. Phospholipase A2 increased the release of beta-End-IR and ACTH-IR. This effect was reversible, concentration-dependent (1-400 ng/ml) and inhibited in calcium-free medium and in the presence of CoCl2 (5 mM) or phospholipase A2 inhibitors (p-bromophenacylbromide, 21 microM; mepacrine, 1 mM). The phospholipase A2-induced beta-End-IR release was accompanied by the release of prostaglandin E2. Inhibition of cyclooxygenase activity by indomethacin (14 or 140 microM) did not change beta-End-IR release induced by phospholipase A2 (5 ng/ml). The effects of blockers of lipoxygenase (nordihydroguaiaretic acid, NDGA; AA861) or lipoxygenase plus cyclooxygenase (BW755C; eicosatetraynoic acid, ETYA) on phospholipase A2-induced release of beta-End-IR were diverse. BW755C (up to 250 microM) and AA861 (up to 100 microM) produced no effect. However, NDGA or ETYA inhibited phospholipase A2-induced beta-End-IR release. NDGA (100 microM) produced a maximum inhibition by about 40% (p less than 0.05), whereas ETYA (100 microM) produced a maximum inhibition by about 85% (p less than 0.001). These data are consistent with the view that phospholipase A2 releases endogenous arachidonic acid which is transformed into products which stimulate ACTH and beta-endorphin release from the corticotrophs; the metabolizing enzyme (possibly a lipoxygenase or epoxygenase) is sensitive to NDGA and especially to ETYA.
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003035:Cobalt / Q000494:pharmacology; D004723:Endorphins / Q000032:analysis / Q000378:metabolism*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010740:Phospholipases / Q000494:pharmacology*; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D011796:Quinacrine / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D001615:beta-Endorphin
chemical_list: D000098:Acetophenones; D001095:Arachidonic Acids; D004723:Endorphins; D016718:Arachidonic Acid; D003035:Cobalt; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine; D007213:Indomethacin