Decreased intracellular calcium stimulates cAMP and renin release from isolated juxtaglomerular (JG) cells.

Abstract

Intracellular calcium and cAMP are the two primary second messengers regulating renin release; cAMP stimulates renin release from juxtaglomerular (JG) cells while increased intracellular calcium inhibits it. We hypothesized that decreased intracellular calcium, which stimulates renin release, acts by stimulating adenylate cyclase, initiating cAMP-mediated renin secretion. We used a primary culture of JG cells isolated from C-57/B6 mice. 70–80% confluent JG cells in serum-free DMEM were incubated for 2 hr with or without (controls) 100 uM of the cytosolic calcium chelator 5′5 dimethyl BAPTA-AM to selectively decrease the intracellular calcium. Measurements of renin release and JG cell cAMP content were determined by radioimmunoassay. Basal renin release in controls was 1,404 ±321 ng AngI/ml/hr/mg prot. Addition of BAPTA-AM increased renin release by 172 ±34 % (p<0.05). The JG cell intracellular cAMP content in untreated controls was 6,198 ±1,770 fmole/ml/mg prot, and was increased 144 ±15% (p<0.05) by BAPTA-AM treatment. Thus, lowering intracellular calcium within the JG cell by chelation resulted in a significant increase in JG cell cAMP content as well as a significant increase in renin release. We conclude that the stimulation of renin induced by lowering the intracellular calcium concentration is due to a subsequent stimulation of adenylate cyclase, increasing the renin-stimulating second messenger cAMP. Supported by NIH RO-1 HL076469.