Identification of a P2Y-purinergic receptor that inhibits adenylyl cyclase.
Identification of a P2Y-purinergic receptor that inhibits adenylyl cyclase.
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发表时间：
1993-12
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通讯作者：
J. Boyer;E. Lazarowski;Xiao-Hua Chen;T. Harden
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作者：
J. Boyer;E. Lazarowski;Xiao-Hua Chen;T. Harden
腺嘌呤核苷酸抑制C6-2B大鼠胶质瘤细胞中异丙肾上腺素和毛喉素刺激的环AMP积累。抑制发生在磷酸二酯酶抑制剂的存在下，腺嘌呤核苷酸的直接测量在完整细胞中的磷酸二酯酶活性没有观察到任何效果。用百日咳毒素预处理C6-2B胶质瘤细胞可阻断P2 Y-嘌呤受体激动剂的抑制作用。一系列ATP和ADP类似物的药理学特异性（2-甲硫基腺苷5 '-三磷酸>或= 2-甲硫基腺苷5'-二磷酸>腺苷5 '-O-（2-硫代二磷酸）> 2-氯-腺苷5'-三磷酸= ADP =腺苷5 '-O-（3-硫代三磷酸）> ATP > UTP）与P2 Y-嘌呤能受体的预期相似; P2 X-嘌呤能受体激动剂，α，β-亚甲基腺苷5 ′-三磷酸和β，γ-亚甲基腺苷5 ′-三磷酸没有作用。由于在许多靶组织中磷脂酶C的激活响应于P2嘌呤能受体的激活而发生，因此在C6-2B细胞中测量了P2 Y受体激动剂对磷酸肌醇积累的影响。在毒蕈碱胆碱能受体激活或AIF 4显著增加肌醇磷酸积累的条件下，未观察到P2 Y嘌呤能受体介导的肌醇脂质代谢调节的证据。这些结果表明，P2嘌呤受体亚型具有不同的信号转导特性存在于C6-2B大鼠胶质瘤细胞。虽然该受体表达磷脂酶C偶联P2 Y-嘌呤能受体的一般药理学特异性，但它可能代表一种独特的受体亚型，因为它抑制腺苷酸环化酶。
Adenine nucleotides inhibited isoproterenol- and forskolin-stimulated cyclic AMP accumulation in C6-2B rat glioma cells. Inhibition occurred in the presence of a phosphodiesterase inhibitor, and no effect of adenine nucleotides was observed in direct measurements of phosphodiesterase activity in intact cells. Pretreatment of C6-2B glioma cells with pertussis toxin blocked the inhibitory effects of P2Y-purinergic receptor agonists. The pharmacological specificity for a series of ATP and ADP analogs (2-methylthioadenosine 5'-triphosphate > or = 2-methylthioadenosine 5'-diphosphate > adenosine 5'-O-(2-thiodiphosphate) > 2-chloro-adenosine 5'-triphosphate = ADP = adenosine 5'-O-(3-thiotriphosphate) > ATP > UTP) was similar to that expected of a P2Y-purinergic receptor; the P2X-purinergic receptor agonists, alpha,beta-methyleneadenosine 5'-triphosphate and beta,gamma-methylene-adenosine 5'-triphosphate, had no effect. Because activation of phospholipase C occurs in response to P2-purinergic receptor activation in many target tissues, the effects of P2Y-receptor agonists on inositol phosphate accumulation were measured in C6-2B cells. No evidence for P2Y-purinergic receptor-mediated regulation of inositol lipid metabolism was observed under conditions where muscarinic cholinergic receptor activation or AIF4-markedly increased inositol phosphate accumulation. These results suggest that a P2-purinergic receptor subtype with distinct signaling properties exists on C6-2B rat glioma cells. Although this receptor expresses the general pharmacological specificity of a phospholipase C-coupled P2Y-purinergic receptor, it may represent a unique receptor subtype since it inhibits adenylyl cyclase.