AJP - Cell Physiology, Vol 263, Issue 6 C1208-C1215, Copyright © 1992 by American Physiological Society
PGE2 regulates cAMP production in cultured rabbit CCD cells: evidence for dual inhibitory mechanisms
T. D. Noland, C. E. Carter, H. R. Jacobson and M. D. Breyer
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
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.
