Brechler V, Jones P W, Levens N R, de Gasparo M, Bottari S P
Cardiovascular Research Department, Pharmaceuticals Division, Ciba-Geigy Ltd., Basel, Switzerland.
Regul Pept. 1993 Mar 19;44(2):207-13. doi: 10.1016/0167-0115(93)90244-3.
Despite some recent reports describing the effects of AT2 receptor selective ligands in vitro and in vivo, the physiological function of this receptor is still a matter of debate. This problem stems amongst others from the difficulty in interpreting results from in vivo experiments with drugs of which it is not known whether they act as agonists or antagonists. We reported earlier that angiotensin II inhibits basal and atrial natriuretic peptide stimulated particulate guanylate cyclase activity through AT2 receptors in PC12W cells. We have used this parameter in intact PC12W cells in order to determine the pharmacological properties of different widely used angiotensin receptor ligands. We found CGP 42112 to behave as a full agonist in this system, whereas PD 123319 and Sar Ile angiotensin II act as antagonists. As expected, the AT1 antagonist losartan did not affect this response.
尽管最近有一些报道描述了AT2受体选择性配体在体外和体内的作用，但该受体的生理功能仍存在争议。这个问题尤其源于难以解释体内实验结果，因为这些实验使用的药物，其是作为激动剂还是拮抗剂尚不清楚。我们之前报道过，血管紧张素II通过PC12W细胞中的AT2受体抑制基础和心房利钠肽刺激的颗粒型鸟苷酸环化酶活性。我们在完整的PC12W细胞中使用这个参数来确定不同广泛使用的血管紧张素受体配体的药理学特性。我们发现CGP 42112在这个系统中表现为完全激动剂，而PD 123319和Sar Ile血管紧张素II则作为拮抗剂。正如预期的那样，AT1拮抗剂氯沙坦不影响这种反应。
