title: Protein kinase C, an endogenous regulator of hormone-induced cyclic AMP induction in porcine luteal cells.
abstract: LH, in addition to increasing cyclic AMP (cAMP) in ovarian cells, stimulates phosphoinositide hydrolysis producing inositol trisphosphate and diacylglycerol (DG). DG activates phospholipid- and calcium-dependent protein kinase (PKC). In the present study, we have used both PKC activators and inhibitors to examine the interactions of the PKC pathway on hormone-induced cAMP production in porcine luteal cells. Phorbol 12-myristate 13-acetate (PMA) enhanced LH- and forskolin-induced cAMP production. A time-course study indicated that the facilitatory effect of PMA was greater when added to incubation tubes following addition LH or forskolin. The non-tumour-promoting phorbol ester 4 alpha-phorbol 12,13-didecanoate, which does not stimulate PKC activation, did not facilitate hormone-induced cAMP induction. PKC inhibitors polymyxin B, sphingosine and 1-(5-isoquinolinesulphonyl)-2-methylpiperazine (H7) antagonized the facilitatory effect of PMA on LH-induced cAMP production. The cAMP induction by both LH and forskolin was inhibited in the presence of PKC inhibitors. Polymyxin E, which differs from polymyxin B by a single amino acid and does not inhibit PKC activation, did not inhibit LH- or forskolin-induced cAMP induction. The results of this study provide evidence for a facilitative action of the PKC effector system on hormonally stimulated cAMP production. Furthermore, PKC may be an important endogenous regulator of adenylate cyclase activity in porcine luteal cells.
authors.affiliation: Department of Obstetrics and Gynecology, University of Saskatchewan, Saskatoon, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Rajkumar
authors.forename: P J
authors.initials: PJ
authors.lastname: Chedrese
authors.forename: H
authors.initials: H
authors.lastname: Ly
authors.forename: B D
authors.initials: BD
authors.lastname: Murphy
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003091:Colistin / Q000494:pharmacology; D003338:Corpus Luteum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis*; D005260:Female; D007546:Isoquinolines / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000502:physiology*; D010703:Phorbol Esters / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D047428:Protein Kinase Inhibitors; D015398:Signal Transduction / Q000502:physiology*; D013110:Sphingosine / Q000494:pharmacology; D013552:Swine / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D007546:Isoquinolines; D010703:Phorbol Esters; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D005576:Colforsin; C008874:phorbol-12,13-diacetate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D007986:Luteinizing Hormone; D000242:Cyclic AMP; D011493:Protein Kinase C; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate; D003091:Colistin