Effects of trifluoperazine on renin secretion of rat kidney slices.
It has been suggested recently that calmodulin acts as an intracellular "Ca-receptor," and that many Ca-dependent cellular activities are mediated in some manner by Ca-calmodulin. The renin-secretory activity of juxtaglomerular cells appears to be inversely related to intracellular Ca concentration (Ca); if Ca-calmodulin is the mediator in the secretory process, it follows that secretory rate should be inversely related to Ca-calmodulin activity. The purpose of these experiments was to determine the effects of trifluoperazine, an inactivator of Ca-calmodulin, on renin secretion of rat kidney slices. Over the range 10(-6) to 10(-4) M, trifluoperazine produced a concentration-dependent increase in renin release. As assessed by lactate dehydrogenase release, the trifluoperazine-induced increase in renin release cannot be attributed to increased cell membrane permeability to proteins. Thus, trifluoperazine stimulated renin secretion in a concentration-dependent manner. This is consistent with an inverse relation between Ca-calmodulin activity and renin secretion. However, in the presence of trifluoperazine, isoproterenol still stimulated and antidiuretic hormone, angiotensin II, high extracellular K concentration, ouabain and vanadate still inhibited renin secretion. Provided these stimulatory and inhibitory effects are associated with decreased and increased Ca, respectively, these observations are inconsistent with the hypothesis that the effects of Ca, on renin secretion are mediated by changes in Ca-calmodulin activity, since increases in Ca promote rather than attenuate the binding of trifluoperazine to calmodulin. It is concluded that trifluoperazine-stimulated renin secretion is mediated by a decrease in Cai produced by inhibition of Ca influx and/or stimulation of Ca efflux and/or sequestration.
D000818:Animals; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000378:metabolism*; D012636:Secretory Rate / Q000187:drug effects; D014268:Trifluoperazine / Q000494:pharmacology*
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D014268:Trifluoperazine; D007770:L-Lactate Dehydrogenase; D012083:Renin