Protein kinase C, an endogenous regulator of hormone-induced cyclic AMP induction in porcine luteal cells.
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.
Rajkumar
K
K
Department of Obstetrics and Gynecology, University of Saskatchewan, Saskatoon, Canada.
Chedrese
P J
PJ
Ly
H
H
Murphy
B D
BD
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
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