Adenosine 1 receptors are expressed by juxtaglomerular cells and interact with calcium signaling to decrease renin release

Adenosine is an important regulator of various functions in the macula densa. Adenosine 1 receptor (A 1 R) agonists have been shown to inhibit renin release from rat renal cortical slices (Churchill et al, AJP , 1987), and plasma reninis significantly greater in A 1 R knockout mice (Persson et al, AJP , 2001 However, there are no reports studying whether these effects are due to direct effects on juxtaglomerular (JG) cells. We hypothesized that JG cells express A 1 R and the activation of JG cell A 1 R inhibits renin release via calcium. To address this question we used primary cultures of JG cells isolated from C57BL/6J. Immunolabeling in JG cells with confocal microscopyfound that cells showing immunofluorescence for renin also labeled for the A 1 R–specificantibody. When we tested A 1 R activation using the selective A 1 R agonist N6‐Cyclohexyladenosine (CHA), it decreased renin release by 25% from 0.35 ±0.14 to 0.27 ±0.12 ug AngI/ml/mg prot (n=5, p <0.005). When we enhanced basal renin by reducing extracellular calcium to 0.2 mM plus EGTA, renin release increased 80% to 0.65 ±0.19 ug AngI/ml/mg prot ( p <0.05). Addition of CHA to this preparation did not decrease renin release, eliminating the A 1 R effect. Our data shows: 1) JG cells express the A 1 R, 2) activation of A 1 R on JG cells inhibits renin release, and 3) their effect on JG cell renin release is mediated at least in part by calcium signaling. Support: NIH 1PO1HL090550‐01