来自睾丸间质细胞瘤的无细胞制剂中鸟嘌呤核苷酸介导的腺苷酸环化酶脱敏作用

Guanine nucleotide mediated desensitization of adenylate cyclase in cell free preparations from a Leydig cell tumour.

作者信息

Levi S N, Schumacher M, Dix C J, Thomas M G, Cooke B A

出版信息

Int J Androl. 1982 Dec;5(6):570-8. doi: 10.1111/j.1365-2605.1982.tb00290.x.

DOI:10.1111/j.1365-2605.1982.tb00290.x

Abstract

Cell free desensitization of a tumour Leydig cell plasma membrane adenylate cyclase has been demonstrated in the presence of guanine nucleotides. In experiments in which the membranes were pre-incubated with various nucleotides and LH, it was shown that this decreased adenylate cyclase activity was dependent on the presence of GTP and occurred both in the presence and absence of ATP. While pre-treatment with LH alone appeared to enhance subsequent adenylate cyclase activity, this hormone was able to potentiate the desensitizing effect of GTP. The desensitizing effect of GTP was not inhibited by sodium fluoride. In contrast, the GTP analogue p(NH)ppG (guanosine 5'beta, gamma-imido triphosphate) caused a persistent activation of the adenylate cyclase. GMP and guanosine also initially inhibited the adenylate cyclase activity, but this was entirely reversed by p(NH)ppG plus LH. GDP in addition to GTP caused desensitization but this was only partially reversed by p(NH)ppG plus LH. It is proposed that in similarity with the ovary (Bockaert et al. 1976; Ezra & Salomon 1982a) desensitization of Leydig tumour cell plasma membrane adenylate cyclase may involve a GTP-mediated phosphorylation step.

摘要

在鸟嘌呤核苷酸存在的情况下，已证实肿瘤间质细胞浆膜腺苷酸环化酶可进行无细胞脱敏。在膜与各种核苷酸和促黄体生成素（LH）预孵育的实验中，结果表明腺苷酸环化酶活性的降低依赖于鸟苷三磷酸（GTP）的存在，且在有和没有三磷酸腺苷（ATP）的情况下均会发生。虽然单独用LH预处理似乎会增强随后的腺苷酸环化酶活性，但这种激素能够增强GTP的脱敏作用。GTP的脱敏作用不受氟化钠抑制。相反，GTP类似物5'-β，γ-亚氨基三磷酸鸟苷（p(NH)ppG）会导致腺苷酸环化酶持续激活。鸟苷酸（GMP）和鸟苷最初也会抑制腺苷酸环化酶活性，但p(NH)ppG加LH可使其完全逆转。除GTP外，二磷酸鸟苷（GDP）也会引起脱敏，但p(NH)ppG加LH只能部分逆转这种情况。有人提出，与卵巢情况类似（博卡特等人，1976年；埃兹拉和萨洛蒙，1982年a），间质细胞瘤细胞膜腺苷酸环化酶的脱敏可能涉及一个GTP介导的磷酸化步骤。