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 < 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 < 0.01) in the presence of MIX. Compared to controls (1.2 mM calcium), AVP-sensitive cAMP accumulation was significantly reduced ( - 34%; P < 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 < 0.01) in the absence of MIX, and similarly by 82% (P < 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.