Calcium-dependent modulation of guanosine 3′,5′-monophosphate in renal cortex: Possible relationship to calcium-dependent release of fatty acid

Abstract

The effects of Ca 2+ on cGMP accumulation in rat renal cortical slices were correlated with the effects on 14C-fatty acid release in tissue prelabeled with 14C arachidonate. Ca 2+ in the presence and absence of ionophore A23187 exerted parallel effects on the release of labeled arachidonate from slices and on slice cGMP content. Thus, Ca 2+ stimulated both arachidonate release and tissue cGMP accumulation 2 to 3-fold when added to slices of renal cortex previously deprived of Ca 2+ and Mg 2+, whereas Mg 2+ had no stimulatory effect on either arachidonate release or tissue cGMP content. In the presence of A23187, Ca 2+ increased arachidonate release and tissue cGMP accumulation 4 to 6-fold. Tetracaine partially inhibited Ca 2+-induced arachidonate release and completely blocked Ca 2+-induced cGMP accumulation. Ca 2+-induced arachidonate release was unaffected by the absence of O 2. Addition of exogenous arachidonate to slices of renal cortex increased tissue cGMP content 2-fold. Linoleate exerted a lesser effect on tissue cGMP, while palmitate and oleate had no effect. Ca 2+- and arachidonateinduced cGMP contents in renal cortical slices were not additive, and both were abolished by exclusion of O 2. Since nitroprusside increased cGMP accumulation 10- to 15-fold in O 2-deprived slices, loss of the Ca 2+ and arachidonate responses under these incubation conditions was selective. Ca 2+-induced cGMP accumulation was unaffected by indomethacin (100 μg/ml), but was abolished by 200 μM 5,8,11,14-eicosatetraynoic acid (TYA). The results are consistent with the possibility that the Ca 2+-dependent processes regulating cGMP in renal cortex include Ca 2+-dependent acyl hydrolase activity, which limits the availability of free polyunsaturated fatty acids. A role for fatty acid oxygenation products in the stimulation of cGMP is suggested, but not established, by the O 2 dependence of the actions of both Ca 2+ and exogenous fatty acids. The failure of exogenous arachidonate or linoleate to mimic quantitatively the actions of Ca 2+ on cGMP may reflect the involvement of other Ca 2+- and O 2-dependent processes in modulation of cGMP in this tissue or limited access of exogenous fatty acid to cGMP regulatory sites in the cell.