Adenosine inhibits renin release from juxtaglomerular cells via an A sub(1) receptor-TRPC-mediated pathway

• Published in: American journal of physiology. Renal physiology 2013-10, Vol.305 (8), p.F1209-F1209
• Main Authors: Ortiz-Capisano, M Cecilia, Atchison, Douglas K, Harding, Pamela, Lasley, Robert D, Beierwaltes, William H
• Format: Article
• Language: English
• Subjects: Adenosine receptors
• ISSN: 1931-857X; 1522-1466

Renin is synthesized and released from juxtaglomerular (JG) cells. Adenosine inhibits renin release via an adenosine A... receptor (A1R) calcium-mediated pathway. How this occurs is unknown. In cardiomyocytes, adenosine increases intracellular calcium via transient receptor potential canonical (TRPC) channels. We hypothesized that adenosine inhibits renin release via A...R activation, opening TRPC channels. However, higher concentrations of adenosine may stimulate renin release through A2R activation. Using primary cultures of isolated mouse JG cells, immunolabeling demonstrated renin and A...R in JG cells, but not A...R subtypes, although RT-PCR indicated the presence of mRNA of both A...AR and A2BR. Incubating JG cells with increasing concentrations of adenosine decreased renin release. Different concentrations of the adenosine receptor agonist N-ethylcarboxamide adenosine (NECA) did not change renin. Activating A...R with 0.5 ...M N6-cyclohexyladenosine (CHA) decreased basal renin release from 0.22 plus or minus 0.05 to 0.14 plus or minus 0.03 ...g of angiotensin I generated per milliliter of sample per hour of incubation (AngI/ml/mg prot) (P < 0.03), and higher concentrations also inhibited renin. Reducing extracellular calcium with EGTA increased renin release (0.35 plus or minus 0.08 ...g AngI/ml/mg prot; P < 0.01), and blocked renin inhibition by CHA (0.28 plus or minus 0.06 ...g AngI/ml/mg prot; P < 0. 005 vs. CHA alone). The intracellular calcium chelator BAPTA-AM increased renin release by 55%, and blocked the inhibitory effect of CHA. Repeating these experiments in JG cells from A1R knockout mice using CHA or NECA demonstrated no effect on renin release. However, RT-PCR showed mRNA from TRPC isoforms 3 and 6 in isolated JG cells. Adding the TRPC blocker SKF-96365 reversed CHA-mediated inhibition of renin release. Thus A1R activation results in a calcium-dependent inhibition of renin release via TRPC-mediated calcium entry, but A2 receptors do not regulate renin release. (ProQuest: ... denotes formulae/symbols omitted.)