Dantrolene stimulates renin secretion by rat renal cortical slices but fails to block calcium-dependent inhibition.
Calcium (Ca) is an inhibitory second messenger in renin secretion, and it has been proposed that some first messengers, such as angiotensin II (A-II), antidiuretic hormone (ADH), and N6-cyclohexyladenosine (CHA), increase Ca and thereby inhibit renin secretion by mobilizing Ca from intracellular sequestration sites. The present experiments were designed to test this proposal by using dantrolene, an antagonist of intracellular Ca mobilization. Dantrolene stimulated renin secretion by rat renal cortical slices in a concentration dependent manner; at 0.0, 0.1, and 0.5 mM dantrolene, secretory rates were 8.1 +/- 0.6, 9.4 +/- 0.6 (p less than 0.05), and 14.9 +/- 1.2 (p less than 0.0001) GU/g x hr, respectively. These results could be interpreted to mean that Ca mobilization is occurring at a finite rate during the basal state, and that by antagonizing this process, dantrolene lowers intracellular Ca and thereby stimulates renin secretion. However, 0.1 mM dantrolene failed to antagonize the inhibitory effects on renin secretion of A-II, ADH, and CHA, and only CHA-induced inhibition of renin secretion was antagonized by 0.5 mM dantrolene. We conclude that if A-II, ADH, and CHA inhibit renin secretion by mobilizing Ca from an intracellular storage site, then the site is insensitive to dantrolene.
Churchill
P C
PC
Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan 48201.
Ellis
V R
VR
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003620:Dantrolene / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000378:metabolism; D007672:Kidney Cortex / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010042:Ouabain / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011188:Potassium / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000378:metabolism*; D013268:Stimulation, Chemical; D013997:Time Factors; D014667:Vasopressins / Q000494:pharmacology
D014667:Vasopressins; D000804:Angiotensin II; C027513:N(6)-cyclohexyladenosine; D010042:Ouabain; D012083:Renin; D003620:Dantrolene; D000241:Adenosine; D011188:Potassium; D002118:Calcium