Inhibition of protein kinase C activity in cultured pituitary cells attenuates both cyclic AMP-independent and -dependent secretion of ACTH.
The present study examines the effect of reduction of protein kinase C (PKC) activity, as induced by either phorbol ester (PMA) down-regulation or staurosporine inhibition, on the secretion of ACTH from cultured anterior pituitary (AP) cells. Short-term (3 h) exposure of cells to 5 nM PMA resulted in almost complete desensitization to both PMA and vasopressin (AVP), while there was only a minor incidence on the effect of corticotropin-releasing factor (CRF). In contrast, long-term (12-24 h) exposure of cells to PMA, as well as pretreatment with staurosporine, dramatically reduced the stimulatory influence of CRF. This was shown not to be due to a decline in ACTH cells' stores, nor to the toxicity of phorbol ester or to a negative autofeedback of ACTH. Pretreatment of corticotrophs with PMA failed to dampen the CRF-induced cyclic AMP formation, while it caused a decline in the effects of forskolin and 8-bromoadenosine cyclic AMP. Stimulated ACTH secretion subsequent to either veratridine- or high K(+)-induced cell depolarization was likewise decreased. We conclude that in corticotrophs the stimulatory action of not only AVP, but also of that of CRF on ACTH secretion strongly relies on PKC activity. In the case of CRF, however, this may not be a primary consequence of receptor occupation, as evidence suggests an indirect relationship which may involve PKC regulation of Ca2+ channels and/or the ion's intracellular messenger function.
Koch
B
B
Institut de Physiologie, URA CNRS 309, Strasbourg, France.
Lutz-Bucher
B
B
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010703:Phorbol Esters / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D000470:Alkaloids; D002273:Carcinogens; D010703:Phorbol Esters; D001127:Arginine Vasopressin; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C008876:phorbol-12,13-didecanoate; D014701:Veratridine; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium