Endothelin inhibits cAMP-induced renin release from isolated renal juxtaglomerular cells

We examined the effects of endothelin (ET)-1, -2, and -3 on renin secretion from cultured mouse renal juxtaglomerular cells. Although different ETs had no consistent effect on basal renin secretion, they equipotently inhibited cAMP-stimulated renin release with an IC50 value of approximately 3 nM. ETs did not significantly affect renin release stimulated by the nitric oxide (NO)-donor nitroprusside (100 microM) or that stimulated by low (2 mM EGTA) or high (3 mM CaCl2) extracellular calcium. The inhibitory effect of ETs on cAMP-dependent renin secretion was abolished by lowering extracellular calcium concentration to the nanomolar range. However, the action of ETs was not changed by the ETA receptor antagonist BQ 123 (100 nM) and was mimicked by the ETB receptor agonists IRL 1620 (1 microM), sarafotoxin S6c (1 microM), and [Ala1,3,11,15]endothelin-1 (4 Ala-ET-1, 1 microM). These findings suggest that ETs selectively inhibit the cAMP-activated pathway of renin secretion through a calcium-sensitive process. The action of ETs on renal juxtaglomerular cells appears to be mediated via ETB receptors.