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...

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Published inThe American journal of physiology Vol. 263; no. 6 Pt 1; p. C1208
Main Authors Noland, T D, Carter, C E, Jacobson, H R, Breyer, M D
Format Journal Article
LanguageEnglish
Published United States 01.12.1992
Subjects
Alkaloids - pharmacology
Animals
Arginine Vasopressin - pharmacology
Cells, Cultured
Cyclic AMP - biosynthesis
Dinoprostone - antagonists & inhibitors
Dinoprostone - pharmacology
Dinoprostone - physiology
Kidney Cortex
Kidney Tubules, Collecting - cytology
Kidney Tubules, Collecting - metabolism
Pertussis Toxin
Prostaglandins - pharmacology
Protein Kinase C - antagonists & inhibitors
Rabbits
Staurosporine
Tetradecanoylphorbol Acetate - pharmacology
Virulence Factors, Bordetella - pharmacology
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Summary: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.
ISSN:0002-9513
DOI:10.1152/ajpcell.1992.263.6.C1208