Juxtaglomerular cell CaSR stimulation decreases renin release via activation of the PLC/IP3 pathway

Abstract

Activation of the calcium (Ca+2)‐sensing receptor (CaSR) on juxtaglomerular (JG) cells results in inhibition of adenylyl cyclase V, decreases in cAMP content and attenuation of renin release. However, the post‐receptor pathway is unknown. In parathyroid glands, the CaSR is coupled to Gq, activating phospholipase C (PLC)/inositol 1,4,5‐trisphosphate (IP3). Thus, we hypothesized JG cell CaSR activation inhibits renin via the PLC/IP3 pathway. Renin release was measured by radioimmunoassay for AngI in the incubation media from isolated mouse JG cells in primary cultures (n = 10 for each). As expected, the CaSR agonist cinacalcet decreased renin release to 56 ± 7% of control (p< 0.001), while the PLC inhibitor U73122 reversed this CaSR‐mediated inhibition of renin by cinacalcet (104 ±11 % of control). The IP3 inhibitor 2‐APB also reversed CaSR‐mediated inhibition of renin from 56 ± 6 to 104 ±11% of control (p< 0.001). We conclude that stimulating JG cell CaSR acts via its coupling with Gq, leading to activation of the PLC/IP3 pathway, inhibiting adenylyl cyclase V, and decreasing renin release. (NIH 5PO1HL090550‐03)