Kurtz A, Della Bruna R, Pfeilschifter J, Bauer C
Physiologisches Institut der Universität Zürich, Switzerland.
Kidney Int. 1988 Apr;33(4):798-803. doi: 10.1038/ki.1988.70.
Adenosine is known to be a potent inhibitor of renin release from the kidneys. The aim of this study was to investigate the transmembrane signalling avenue that the second messenger of adenosine causes inhibition of renal renin release. Using short term cultures of juxtaglomerular cells isolated from rat kidneys, we found that adenosine inhibited spontaneous renin release from these cells up to 40% of control, in a dose dependent fashion between 10(-10) M to 10(-6) M. Half maximal inhibition was observed at 2 X 10(-8) M adenosine. The inhibitory effect of adenosine on renin release could be mimicked by the A1-receptor agonist N6-cyclohexyladenosine (CHA) and could be attenuated by the A-receptor antagonist theophylline (5 X 10(-5) M). The A2-receptor agonist 5'-N-ethylcarboxamideadenosine (NECA) had no inhibitory effect on renin release. These findings indicate that the inhibitory effect of adenosine is mediated by A1-receptors on juxtaglomerular cells. Adenosine had no effect on either transmembrane calcium influx or the cytosolic free calcium concentration in the isolated juxtaglomerular cells. Adenosine also did not alter the cellular level of cyclic AMP in the concentration range employed. However, adenosine led to a dose dependent increase of the cellular level of cyclic GMP. Half maximal increase of cGMP was observed at 10(-8) M adenosine. The effect of adenosine on cyclic GMP could be mimicked by the A1-receptor agonist CHA and could be attenuated by the A-receptor antagonist, theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)
已知腺苷是肾脏肾素释放的强效抑制剂。本研究的目的是探究腺苷的第二信使导致肾脏肾素释放受抑制的跨膜信号传导途径。使用从大鼠肾脏分离的肾小球旁细胞进行短期培养，我们发现腺苷以剂量依赖方式（10⁻¹⁰ M至10⁻⁶ M）抑制这些细胞的自发性肾素释放，最高可达对照的40%。在2×10⁻⁸ M腺苷时观察到半数最大抑制。腺苷对肾素释放的抑制作用可被A1受体激动剂N6 - 环己基腺苷（CHA）模拟，并可被A受体拮抗剂茶碱（5×10⁻⁵ M）减弱。A2受体激动剂5'-N - 乙基羧酰胺腺苷（NECA）对肾素释放无抑制作用。这些发现表明腺苷的抑制作用是由肾小球旁细胞上的A1受体介导的。腺苷对分离的肾小球旁细胞的跨膜钙内流或胞质游离钙浓度均无影响。在所采用的浓度范围内，腺苷也未改变细胞内环磷酸腺苷（cAMP）水平。然而，腺苷导致细胞内环磷酸鸟苷（cGMP）水平呈剂量依赖性增加。在腺苷浓度为10⁻⁸ M时观察到cGMP的半数最大增加。腺苷对cGMP的作用可被A1受体激动剂CHA模拟，并可被A受体拮抗剂茶碱减弱。（摘要截短于250字）
