Noronha-Blob L, Marshall R P, Kinnier W J, U'Prichard D C
Life Sci. 1986 Sep 22;39(12):1059-67. doi: 10.1016/0024-3205(86)90197-9.
The PC12 cell line, a clone isolated from a pheochromocytoma tumor of rat adrenal medulla, was shown to exclusively contain stimulatory adenosine (A2) receptors linked to adenylate cyclase (AC). AC was stimulated 6-7 fold by several agonists with a rank order of potency of 5'-N-Ethyl carboxamidoadenosine (NECA) greater than 2-Chloroadenosine (2-CADO) greater than (R)-N-Phenylisopropyladenosine (R-(-)-PIA) greater than N6-Cyclopentyladenosine (CPA) greater than N6-Cyclohexyladenosine (CHA) greater than S-(+)-PIA. AC activity was antagonized by a variety of adenosine receptor antagonists with a potency order of 1,3,-Dipropyl-8-(2-amino-4-chlorophenyl)xanthine (PACPX) greater than 1,3,-Diethyl-8-phenylxanthine (DPX) greater than 8-Phenyltheophylline greater than 3-Isobutyl-1-methylxanthine (IBMX) greater than 8-(p-sulfophenyl)theophylline (PST) greater than 7-(beta-chloroethyl)theophylline greater than theophylline = enprofylline = caffeine. Under conditions known to favour receptor-mediated Ni-coupled inhibition of AC, R-(-)-PIA failed to inhibit both basal and forskolin stimulated AC activity in PC12 cells, confirming the absence of an A1 mediated response. On the other hand, adenosine agonists inhibited AC activity in rat cortical membranes with a rank order of potency of CPA greater than R-(-)-PIA greater than CHA greater than NECA greater than S-(+)-PIA greater than 2-CADO. These findings suggest that PC12 cells are functionally deficient in an A1 receptor linked AC response but are efficiently coupled to A2 stimulatory receptors. The cells should prove useful for further study of A2 adenosine receptors and to establish selectivity profiles of compounds acting at both A1 and A2 receptors.
PC12细胞系是从大鼠肾上腺髓质嗜铬细胞瘤中分离出的一个克隆，已证明其仅含有与腺苷酸环化酶（AC）相连的刺激性腺苷（A2）受体。几种激动剂可使AC活性增强6至7倍，其效力顺序为5'-N-乙基羧酰胺基腺苷（NECA）＞2-氯腺苷（2-CADO）＞（R）-N-苯基异丙基腺苷（R-(-)-PIA）＞N6-环戊基腺苷（CPA）＞N6-环己基腺苷（CHA）＞S-(+)-PIA。AC活性受到多种腺苷受体拮抗剂的拮抗，其效力顺序为1,3-二丙基-8-(2-氨基-4-氯苯基)黄嘌呤（PACPX）＞1,3-二乙基-8-苯基黄嘌呤（DPX）＞8-苯基茶碱＞3-异丁基-1-甲基黄嘌呤（IBMX）＞8-(对磺基苯基)茶碱（PST）＞7-(β-氯乙基)茶碱＞茶碱 = 恩丙茶碱 = 咖啡因。在已知有利于受体介导的Ni偶联抑制AC的条件下，R-(-)-PIA未能抑制PC12细胞中的基础AC活性和福斯高林刺激的AC活性，证实不存在A1介导的反应。另一方面，腺苷激动剂抑制大鼠皮质膜中的AC活性，其效力顺序为CPA＞R-(-)-PIA＞CHA＞NECA＞S-(+)-PIA＞2-CADO。这些发现表明，PC12细胞在与A1受体相连的AC反应中功能缺陷，但能有效地与A2刺激性受体偶联。这些细胞应有助于进一步研究A2腺苷受体，并建立作用于A1和A2受体的化合物的选择性概况。
