PGE2 regulates cAMP production in cultured rabbit CCD cells: evidence for dual inhibitory mechanisms.
In cultured cortical collecting duct (CCD) cells, exogenous prostaglandin E2 (PGE2) inhibited arginine vasopressin (AVP)-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production in a concentration-dependent manner. Although pertussis toxin (PT, 500 ng/ml) alone did not reverse the PGE2-dependent inhibition, PT and staurosporine, a protein kinase C inhibitor, together partially reversed the effect of exogenous PGE2. In contrast, PT completely reversed the inhibition of AVP-dependent cAMP production by sulprostone. These data suggest that exogenous PGE2 can inhibit AVP-stimulated cAMP production and that the inhibitory effects of PGE2 are mediated by staurosporine- and PT-sensitive component(s). Short-term (15-240 min) incubation with phorbol 12-myristate 13-acetate (PMA, 10(-7) M) inhibited PGE2-stimulated cAMP production. Long-term (20 h) incubation with PMA augmented PGE2-stimulated cAMP production. These data provide evidence for the maintenance of a PT-sensitive PGE2-dependent inhibitory pathway of cAMP production in cultured CCD cells. In addition, data are presented that support an inhibitory role for protein kinase C in the effects of PGE2 on the metabolism of cAMP in these cells.
Noland
T D
TD
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
Carter
C E
CE
Jacobson
H R
HR
Breyer
M D
MD
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis*; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D007672:Kidney Cortex; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism*; D037342:Pertussis Toxin; D011453:Prostaglandins / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011817:Rabbits; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000470:Alkaloids; D011453:Prostaglandins; D010566:Virulence Factors, Bordetella; D001127:Arginine Vasopressin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D011493:Protein Kinase C; D019311:Staurosporine; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate