Calcium-dependent modulation of guanosine 3',5'-monophosphate in renal cortex. Possible relationship to calcium-dependent release of fatty acid.
The effects of Ca(2+) on cGMP accumulation in rat renal cortical slices were correlated with the effects on (14)C-fatty acid release in tissue prelabeled with (14)C 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 microg/ml), but was abolished by 200 microM 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.
Department of Medicine, Veterans Adminstration Medical Center and University of Pittsburgh, Pittsburgh, PA 15240, USA.
R G
RG
Briggs
F R
FR
Derubertis
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D007672:Kidney Cortex / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005227:Fatty Acids; D006152:Cyclic GMP; D002118:Calcium