Rossi N, Churchill P, Ellis V, Amore B
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201.
Am J Physiol. 1988 Oct;255(4 Pt 2):H885-90. doi: 10.1152/ajpheart.1988.255.4.H885.
Adenosine analogues selective for the A1 subclass of adenosine receptors, such as N6-cyclohexyladenosine (CHA), induce vasoconstriction in the isolated rat kidney perfused at constant flow. Presumably, the vasoconstriction is mediated by increased Ca2+ concentration in renal vascular smooth muscle cells, but the mechanism by which A1 adenosine receptor occupation leads to increased Ca2+ is unknown. In the present experiments, the isolated, perfused rat kidney vasoconstricted in response to CHA, to K depolarization, and to BAY K 8644 (a Ca2+ channel agonist). All of these responses were completely blocked by methoxyverapamil, which suggests that CHA, like K depolarization and BAY K 8644, induces renal vasoconstriction by increasing Ca2+ influx through potential operated Ca2+ channels. The mechanism of action of CHA was different, however, in that pertussis toxin treatment blocked the response to CHA without affecting the responses to K depolarization or to BAY K 8644. Therefore, a pertussis toxin-sensitive step must intervene between occupation of A1 adenosine receptors on renal vascular smooth muscle cells and increased Ca2+ influx through potential-operated Ca2+ channels.
对腺苷受体A1亚类具有选择性的腺苷类似物，如N6 - 环己基腺苷（CHA），在以恒定流量灌注的离体大鼠肾脏中可诱导血管收缩。据推测，这种血管收缩是由肾血管平滑肌细胞中Ca2+浓度升高介导的，但A1腺苷受体被占据导致Ca2+升高的机制尚不清楚。在本实验中，离体灌注的大鼠肾脏对CHA、K去极化和BAY K 8644（一种Ca2+通道激动剂）产生血管收缩反应。所有这些反应均被甲氧维拉帕米完全阻断，这表明CHA与K去极化和BAY K 8644一样，通过增加Ca2+经电压门控Ca2+通道内流来诱导肾血管收缩。然而，CHA的作用机制有所不同，因为百日咳毒素处理可阻断对CHA的反应，而不影响对K去极化或BAY K 8644的反应。因此，在肾血管平滑肌细胞上A1腺苷受体被占据与Ca2+经电压门控Ca2+通道内流增加之间，必定存在一个对百日咳毒素敏感的步骤。
