Lin M C, Welton A F, Berman M F
J Cyclic Nucleotide Res. 1978 Jun;4(3):159-68.
Expression of activation of rat liver adenylate cyclase by the A1 peptide of cholera toxin and NAD is dependent on GTP. The nucleotide is effective either when added to the assay medium or during toxin (and NAD) treatment. Toxin treatment increases the Vmax for activation by GTP and the effect of GTP persists in toxin-treated membranes, a property seen in control membranes only with non-hydrolyzable analogs of GTP such as Gpp(NH)p. These observations could be explained by a recent report that cholera toxin acts to inhibit a GTPase associated with denylate cyclase. However, we have observed that one of the major effects of the toxin is to decrease the affinity of guanine nucleotides for the processes involved in the activation of adenylate cyclase and in the regulation of the binding of glucagon to its receptor. Moreover, the absence of lag time in the activation of adenylate cyclase by GTP, in contrast to by Gpp(NH)p, and the markedly reduced fluoride action after toxin treatment suggest that GTPase inhibition may not be the only action of cholera toxin on the adenylate cyclase system. We believe that the multiple effects of toxin action is a reflection of the recently revealed complexity of the regulation of adenylate cyclase by guanine nucleotides.
霍乱毒素的A1肽和NAD对大鼠肝腺苷酸环化酶的激活作用依赖于GTP。该核苷酸在添加到测定介质中或在毒素（和NAD）处理期间均有效。毒素处理增加了GTP激活的Vmax，并且GTP的作用在毒素处理的膜中持续存在，这种特性仅在对照膜中使用GTP的不可水解类似物如Gpp(NH)p时才可见。这些观察结果可以用最近的一份报告来解释，即霍乱毒素的作用是抑制与腺苷酸环化酶相关的GTP酶。然而，我们观察到毒素的主要作用之一是降低鸟嘌呤核苷酸对参与腺苷酸环化酶激活和胰高血糖素与其受体结合调节过程的亲和力。此外，与Gpp(NH)p不同，GTP激活腺苷酸环化酶时没有延迟时间，并且毒素处理后氟化物的作用明显降低，这表明GTP酶抑制可能不是霍乱毒素对腺苷酸环化酶系统的唯一作用。我们认为毒素作用的多种效应反映了最近揭示的鸟嘌呤核苷酸对腺苷酸环化酶调节的复杂性。
