Importance of calcium in renal renin release.
The sequence of intracellular events that lead to renin release is incompletely defined. Accordingly, we examined the interrelationship of two important factors in the process: renin release coupled to cAMP and renin release related to a decrease in intracellular calcium activity (Cai). Rat renal cortical slices were used to study these relationships in vitro. In the initial studies, cAMP-coupled renin release was established for isoproterenol (10(-5) M), prostacyclin (PGI2; 10(-6) M), and forskolin (10(-5) M). Each agent caused an increase in renin release and tissue cAMP levels, which were inhibited by the addition of the adenyl cyclase inhibitor 2',5'-dideoxyadenosine (DDA, 10(-5) M) to the media. Diltiazem (10(-4) M) and 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8; 0.6 X 10(-4) M) are believed to decrease Cai by different mechanisms; each of these agents caused a significant increase in renin release. Renin release stimulated by diltiazem, and TMB-8 was not inhibited by either DDA or indomethacin. The calcium ionophore A23187 (17 X 10(-6) M) and vanadate (10(-3) M) were next added to produce an increase in Cai. Both of these agents blunted renin release produced by isoproterenol, PGI2, and forskolin. These results provide strong indirect support for an inverse relationship between Cai and renin release in the juxtaglomerular cell. The results also imply that changes in Cai occupy a step that is distal to cAMP-coupled events in the sequence of intracellular events which culminate in renin release.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003634:DDT / Q000031:analogs & derivatives / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007606:Juxtaglomerular Apparatus / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects; D008297:Male; D051381:Rats; D012083:Renin / Q000378:metabolism*; D012084:Renin-Angiotensin System; D013268:Stimulation, Chemical
D005576:Colforsin; D000001:Calcimycin; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; C000849:bis(p-chlorophenyl)acetic acid; D003634:DDT; D011464:Epoprostenol; D000242:Cyclic AMP; D012083:Renin; D004110:Diltiazem; D007545:Isoproterenol; D002118:Calcium