Prostaglandins mediate the defect in AVP-stimulated cAMP generation in immature collecting duct.
The immature kidney is characterized by resistance to arginine vasopressin (AVP). In the immature cortical collecting duct (iCCD), AVP-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) generation is decreased, but the mechanisms involved are not known. We examined cAMP production in isolated CCD from immature and mature rabbits. Cellular cAMP levels were measured by radioimmunoassay under basal conditions and after stimulation with hormone. Basal cAMP production in the iCCD was not different from that in the mature CCD (mCCD). In contrast, AVP- and forskolin-stimulated cAMP generation were severely decreased in the iCCD. Inhibition of endogenous prostaglandin production by indomethacin increased AVP-stimulated cAMP generation in the iCCD to levels that were not different from the mCCD. Inhibition of protein kinase C (PKC) by staurosporine and inhibition of Gi by pertussis toxin elicited a mature cAMP response in the iCCD. These data suggest that the defect in AVP-stimulated cAMP production in the iCCD is mediated by prostaglandins via 1) activation of Gi and 2) direct inhibition of the adenylyl cyclase catalytic subunit. In addition, PKC appears to play a significant role.
Bonilla-Felix
M
M
Department of Pediatrics, University of Texas Health Science Center at Houston 77030.
John-Phillip
C
C
D000262:Adenylyl Cyclases / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001127:Arginine Vasopressin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis*; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D011453:Prostaglandins / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D011817:Rabbits
D011453:Prostaglandins; D011506:Proteins; D001127:Arginine Vasopressin; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D015232:Dinoprostone