Avkiran M, Yokoyama H
Centre for Cardiovascular Biology and Medicine, King's College London, The Rayne Institute, St Thomas' Hospital, London SE1 7EH.
Br J Pharmacol. 2000 Oct;131(4):659-62. doi: 10.1038/sj.bjp.0703647.
Sarcolemmal Na(+)/H(+) exchanger (NHE) activity is increased by stimulation of G(q) protein-coupled receptors (G(q)PCRs), but the roles of other GPCRs are largely unknown. We determined the effects of N-[(1S,trans)-2-hydroxycyclopentyl]adenosine (GR79236), a selective agonist of the G(i)PCR adenosine A(1) receptor, on sarcolemmal NHE activity in adult rat ventricular myocytes (n=8-10 per group). NHE activity was indexed by the H(+) efflux rate after intracellular acidification, measured by microepifluorescence. GR79236 alone (0.01-10 microM) had no effect on NHE activity. However, co-administration of GR79236 inhibited, in a concentration-dependent manner, the stimulation of NHE activity by the alpha(1)-adrenoceptor agonist phenylephrine (10 microM). The inhibitory effect of GR79236 (10 microM) was abolished by (1) the selective A(1) antagonist 1,3-dipropyl-8-cyclopentylxanthine (0.1 microM), confirming an A(1) receptor-mediated action, and (2) pre-treatment with pertussis toxin (5 microgram ml(-1) for 60 min), indicating a G(i) protein-mediated mechanism. Our data suggest the existence of inhibitory crosstalk between the G(i)PCR adenosine A(1) receptor and the G(q)PCR alpha(1)-adrenoceptor in the regulation of sarcolemmal NHE activity.
肌膜Na(+)/H(+)交换体（NHE）的活性可通过刺激G(q)蛋白偶联受体（G(q)PCRs）而增强，但其他GPCRs的作用在很大程度上尚不清楚。我们测定了G(i)PCR腺苷A(1)受体的选择性激动剂N-[(1S,反式)-2-羟基环戊基]腺苷（GR79236）对成年大鼠心室肌细胞（每组n = 8 - 10）肌膜NHE活性的影响。通过微差荧光测定细胞内酸化后的H(+)外流速率来衡量NHE活性。单独使用GR79236（0.01 - 10 μM）对NHE活性无影响。然而，联合使用GR79236可浓度依赖性地抑制α(1)-肾上腺素能受体激动剂去氧肾上腺素（10 μM）对NHE活性的刺激。GR79236（10 μM）的抑制作用可被以下因素消除：（1）选择性A(1)拮抗剂1,3 - 二丙基 - 8 - 环戊基黄嘌呤（0.1 μM），证实是A(1)受体介导的作用；（2）用百日咳毒素（5 μg ml(-1)处理60分钟）预处理，表明是G(i)蛋白介导的机制。我们的数据表明，在肌膜NHE活性的调节中，G(i)PCR腺苷A(1)受体和G(q)PCRα(1)-肾上腺素能受体之间存在抑制性串扰。
