Modulation of vasopressin-sensitive cyclic AMP levels by calcium in papillary collecting tubules.
The present study was designed to examine the extent to which calcium modulates vasopressin (AVP)-stimulated cyclic AMP (cAMP) accumulation in microdissected rat papillary collecting ducts (PCD), and to identify the mechanism(s) involved. Using a submaximal concentration of vasopressin (1 nM), ionophore A23187-mediated increases in intracellular calcium inhibited AVP-dependent cAMP levels by 69% (P less than 0.001) in the absence of the cAMP-phosphodiesterase inhibitor 1-methyl-3-isobutyl xanthine (MIX). The degree of inhibition was significantly reduced (-47%; P less than 0.01) in the presence of MIX. Compared to controls (1.2 mM calcium), AVP-sensitive cAMP accumulation was significantly reduced (-34%; P less than 0.05) when PCD were incubated in a medium containing an increased (5.0 mM) calcium concentration. In the presence of MIX 5.0 mM calcium had no effect on cAMP levels. Conversely, compared to controls, a calcium-free medium increased AVP-dependent cAMP accumulation by 89% (P less than 0.01) in the absence of MIX, and similarly by 82% (P less than 0.05) in the presence of MIX. These data demonstrate that calcium can modulate AVP-dependent cAMP accumulation in PCD as a result of effects on both adenylate cyclase and cAMP phosphodiesterase activities.
Jackson
B A
BA
Department of Physiology and Biophysics, University of Kentucky, College of Medicine, Lexington 40536-0084.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002118:Calcium / Q000032:analysis / Q000494:pharmacology*; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism*; D003593:Cytoplasm / Q000032:analysis; D007679:Kidney Medulla / Q000187:drug effects* / Q000201:enzymology; D007684:Kidney Tubules / Q000187:drug effects*; D007685:Kidney Tubules, Collecting / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D001127:Arginine Vasopressin; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D002118:Calcium