Vasopressin, unlike phorbol ester, fails to synergistically interact with pituitary adenylate cyclase activating polypeptide (PACAP) in stimulating cyclic AMP formation and ACTH secretion in cultured anterior pituitary cells.
In an attempt to determine if PACAP synergistically interacts with vasopressin (VP) and protein kinase C (PKC) to enhance cyclic AMP formation and adrenocorticotrophic hormone (ACTH) secretion, the effects of PACAP, either alone or together with VP and the phorbol ester phorbol 12-myristate 13-acetate (PMA) were examined in primary cultures of rat anterior pituitary cells. VP failed to potentiate the stimulatory effect of PACAP on cyclic AMP formation, while it dramatically enhanced the effect of corticotropin-releasing factor (CRF). However, activation of PKC upon exposure of cells to PMA amplified cyclic AMP production induced by both peptides, though in the case of PACAP, contrary to that of CRF, potentiation was markedly dependent on the blockade of phosphodiesterase (PDE) activity, for it was undetectable in the absence of the inhibitor Rolipram. Depletion of PKC by long-term treatment of pituitary cells with PMA abolished the synergistic influence of PMA. There was no significant effect of PACAP, either alone or together with PMA, on ACTH secretion, while PMA enhanced peptide secretion elicited by CRF. The data show that in anterior pituitary cells cyclic AMP accumulation induced by PACAP and CRF was differentially modulated by PKC and PDE activities and that the potentiation of PACAP-stimulated cyclic AMP accumulation by PMA was not reflected by parallel increment of ACTH secretion.
Institut de Physiologie, URA 1446 CNRS, Strasbourg, France.
B
B
Koch
B
B
Lutz-Bucher
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D004347:Drug Interactions; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020889:Rolipram; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
C495403:Adcyap1 protein, rat; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011760:Pyrrolidinones; D001127:Arginine Vasopressin; D005576:Colforsin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D011493:Protein Kinase C; D020889:Rolipram; D013755:Tetradecanoylphorbol Acetate