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.
Briggs
R G
RG
Department of Medicine, Veterans Adminstration Medical Center and University of Pittsburgh, Pittsburgh, PA 15240, USA.
Derubertis
F R
FR
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