Mechanism of release of beta-endorphin from rat pituitary cells. Role of lipoxygenase products of arachidonic acid.
We investigated the effects of metabolites of arachidonic acid on the release of beta-endorphin-like immunoreactivity (beta-end-IR) from rat anterior pituitary cells. Anterior pituitary cells from female rats cultured with arachidonic acid released beta-end-IR in a dose- and time-dependent manner. To determine which metabolites of arachidonic acid stimulated the release of beta-end-IR, we examined the effects of an inhibitor of the cyclooxygenase, indomethacin, and an inhibitor of the 5-lipoxygenase, 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA-861). beta-end-IR release from pituitary cells induced by arachidonic acid was inhibited about 37% by AA-861, but was not affected by indomethacin. Other lipoxygenase inhibitors (eicosatetraynoic and nordihydroguaiaretic acid) also reduced the release of beta-end-IR induced by arachidonic acid. The effects of the 5-lipoxygenase products 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) and leukotrienes (LTA4, B4, C4, and D4) on the release of beta-end-IR from rat pituitary cells were also examined. 5-HETE (1-50 microM) elicited a dose-dependent release of beta-end-IR from cultured pituitary cells, and 50 microM 5-HETE induced beta-endorphin release time dependently. LTA4 and LTB4 also significantly stimulated the release of beta-end-IR, but LTC4 and LTD4 had no effect. Other lipoxygenase products (12-hydroxy-5,8,10,14-eicosatetraenoic acid, 12-HETE; 15-hydroxy-5,8,10,14-eicosatetraenoic acid, 15-HETE) were also secretagogues at concentrations of above 1 microM.(ABSTRACT TRUNCATED AT 250 WORDS)
Nishizaki
T
T
Department of Obstetrics and Gynecology, Osaka University Medical School, Japan.
Ikegami
H
H
Tasaka
K
K
Hirota
K
K
Miyake
A
A
Tanizawa
O
O
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism* / Q000494:pharmacology; D016227:Benzoquinones; D001696:Biomechanical Phenomena; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D015289:Leukotrienes / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D011809:Quinones / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D001615:beta-Endorphin / Q000378:metabolism*
D001095:Arachidonic Acids; D016227:Benzoquinones; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D011809:Quinones; D016718:Arachidonic Acid; D001615:beta-Endorphin; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D008084:Lipoxygenase; D007213:Indomethacin