Gilfillan A M, Rooney S A
J Pharmacol Exp Ther. 1987 Jun;241(3):907-14.
We examined the effects of P1 purinoceptor agonists on secretion of phosphatidylcholine in primary cultures of rat type II pneumocytes. Adenosine and its nonmetabolizable analogs, 5'-N-ethylcarboxyamidoadenosine (NECA), N6-phenylisopropyladenosine (PIA) and 2-chloroadenosine, increased secretion, and this effect was dependent on concentration. At the highest concentration, all agonists stimulated phosphatidylcholine secretion approximately 2-fold. NECA, with an EC50 of 8.9 X 10(-8) M, was the most potent agonist. The order of potency was NECA greater than 2-chloroadenosine = L-PIA greater than or equal to adenosine greater than D-PIA. The stimulatory effect of 10(-6) M NECA was diminished by the P1 antagonists theophylline and 8-phenyltheophylline. The degree of stimulation by the adenosine analogs as well as its time course was the same as that induced by terbutaline. The effects of the adenosine analogs and of terbutaline were not additive, suggesting a similar mode of action for the beta adrenergic and purinoceptor agonists. Terbutaline and the adenosine analogs increased intracellular cyclic AMP levels. Again, NECA was the most potent adenosine analog. For NECA, L-PIA and adenosine, there was a significant correlation between effects on secretion and on cyclic AMP content. These data suggest that the effect of adenosine on phosphatidylcholine secretion in type II pneumocytes is mediated by the A2 subtype of the P1 purinoceptor.
我们研究了P1嘌呤受体激动剂对大鼠II型肺细胞原代培养物中磷脂酰胆碱分泌的影响。腺苷及其不可代谢类似物5'-N-乙基甲酰胺基腺苷（NECA）、N6-苯异丙基腺苷（PIA）和2-氯腺苷可增加分泌，且这种作用依赖于浓度。在最高浓度时，所有激动剂均可刺激磷脂酰胆碱分泌增加约2倍。NECA的EC50为8.9×10(-8) M，是最有效的激动剂。效力顺序为NECA＞2-氯腺苷 = L-PIA≥腺苷＞D-PIA。P1拮抗剂茶碱和8-苯基茶碱可减弱10(-6) M NECA的刺激作用。腺苷类似物的刺激程度及其时间进程与特布他林诱导的相同。腺苷类似物和特布他林的作用并非相加性的，提示β肾上腺素能和嘌呤受体激动剂的作用模式相似。特布他林和腺苷类似物可增加细胞内环磷酸腺苷水平。同样，NECA是最有效的腺苷类似物。对于NECA, L-PIA和腺苷，其对分泌和环磷酸腺苷含量的影响之间存在显著相关性。这些数据表明，腺苷对II型肺细胞中磷脂酰胆碱分泌的作用是由P1嘌呤受体的A2亚型介导的。
