TRPC channels are involved in endothelin 1 mediated inhibition of renin release from juxtaglomerular cells (1095.12)

Abstract

Renin is produced by, stored in and released by juxtaglomerular (JG) cells. Increases in intracellular calcium (Ca) decrease renin release. I’ve found that JG cells contain multiple isoforms of canonical transient receptor potential (TRPC) Ca‐permeable channels. Among those, TRPC1, 4 and 5, are known to function as store‐operated Ca channels. Endothelin (ET)1 binds to G‐coupled protein receptors whose activation leads to a phospholipase C (PLC)/ IP3 signaling pathway, potentially stimulating store‐operated Ca channels. I hypothesized that endothelin inhibits renin release by activating TRPC store‐operated Ca channels. RT‐ PCR revealed expression of both ETA and ETB receptors in freshly isolated mouse JG cells. Incubation of primary cultures of JG cells with ET1 (10nM) decreased renin release by 28% from 0.84±0.07 to 0.60±0.07 µg ANGI/ml/hr/mg prot. (p<0.001). An IP3 blocker (2APB, 0.1mM) returned renin release back to control. Addition of the TRPC blocker (SKF 96365, 50µM) completely reversed the Ca‐mediated inhibition of renin release by ET1 to 0.99±0.07 µg ANGI/ml/hr/mg prot. These results suggest that 1) JG cells express ETA and ETB receptors, 2) ET1 mediates inhibition of renin release in JG cells by activation of ETA or ETB receptors and subsequent PLC/IP3 signaling cascade activation, and 3) ET receptors link ET1 and TRPC store‐operated Ca channels to mediate ET1‐mediated Ca inhibition of renin release.Grant Funding Source: NIH 5PO1HL090550‐03