Differential involvement of phospholipase A2 in phorbol ester-induced luteinizing hormone and growth hormone release from rat anterior pituitary tissue.
The protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu) induced the release of both luteinizing hormone (LH) and growth hormone (GH) from proestrous rat anterior pituitary pieces in vitro. Phorbol 12,13-dibutyrate-induced LH, but not GH release was readily inhibited by the phospholipase A2 (PLA2) inhibitors, quinacrine, aristolochic acid, ONO-RS-082 and chloracysine. Furthermore, PDBu induced release of [3H]arachidonic acid ([3H]AA) from pre-labelled anterior pituitary tissue that was prevented in the presence of quinacrine, aristolochic acid and ONO-RS-082 but not the diglyceride lipase inhibitor RHC 80267. The effect of PDBu was completely inhibited by staurosporine and the selective PKC inhibitor Ro 31-8220 but only partially by low concentrations of H7; consistent with the involvement of both H7-sensitive and H7-resistant forms of PKC in the activation of PLA2 by PDBu. The protein synthesis inhibitor cycloheximide inhibited the release of both [3H]AA and LH that had been induced by PDBu, whereas LH release induced by the PLA2 activator mellitin was cycloheximide-insensitive. These results suggest that PKC activators may induce LH but not GH release from anterior pituitary tissue by a mechanism involving activation of a PLA2, brought about by a process which is reliant on protein synthesis.
Thomson
F J
FJ
MRC Brain Metabolism Unit, University Department of Pharmacology, Edinburgh, UK.
Mitchell
R
R
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D062365:Aminobenzoates / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D034341:Aristolochic Acids; D002723:Chlorobenzoates; D002934:Cinnamates / Q000494:pharmacology; D003512:Cyclohexanones / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism*; D008555:Melitten / Q000494:pharmacology; D010616:Phenanthrenes / Q000494:pharmacology; D010640:Phenothiazines / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000502:physiology*; D054467:Phospholipases A2; D010879:Piperazines / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011359:Proestrus; D011493:Protein Kinase C / Q000378:metabolism; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine; D062367:ortho-Aminobenzoates
D000470:Alkaloids; D062365:Aminobenzoates; D034341:Aristolochic Acids; D002723:Chlorobenzoates; D002934:Cinnamates; D003512:Cyclohexanones; D007211:Indoles; D007546:Isoquinolines; D010616:Phenanthrenes; D010640:Phenothiazines; D010879:Piperazines; D062367:ortho-Aminobenzoates; D008555:Melitten; D016718:Arachidonic Acid; D015240:Phorbol 12,13-Dibutyrate; D015759:Ionomycin; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D007986:Luteinizing Hormone; D013006:Growth Hormone; C000228:aristolochic acid I; D003513:Cycloheximide; C060048:2-(4-amylcinnamoyl)amino-4-chlorobenzoic acid; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine; D019311:Staurosporine; C004584:chloracizine; C064758:Ro 31-8220