Receptors that couple to 2 classes of G proteins increase cAMP and activate CFTR expressed in Xenopus oocytes.
Receptors that couple to 2 classes of G proteins increase cAMP and activate CFTR expressed in Xenopus oocytes.
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与 2 类 G 蛋白偶联的受体会增加 cAMP 并激活非洲爪蟾卵母细胞中表达的 CFTR。
DOI：
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发表时间：
1993
期刊：
影响因子：
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通讯作者：
Norman Davidson
中科院分区：
文献类型：
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作者：
Y. Uezono;Jonathan Bradley;Churl Min;N. McCarty;Michael W. Quick;J. Riordan;C. Chavkin;K. Zinn;Henry A. Lester;Norman Davidson
囊性纤维化跨膜传导调节因子（CFTR）是一种被磷酸化激活的Cl-通道，在非洲爪蟾卵母细胞中与cAMP信号通路的其他几种组分的各种组合一起表达。激活共表达的β 2肾上腺素能受体增加cAMP并导致CFTR激活。CFTR的激活(1)只需要短时间（15秒）暴露于异丙肾上腺素中，(2)在激动剂浓度比放射免疫测定法检测到的产生cAMP增加的激动剂浓度低100-1000倍的情况下发生，(3)每个卵母细胞只需要注射5pg受体cRNA，(4)可以通过腺苷酸环化酶II型或III型或Gs α的cRNA共表达进一步增加。此外，CFTR激活和β 2激活引起的cAMP增加通过激活共表达的5HT1A受体而增强，该受体被认为与Gi偶联。II型腺苷酸环化酶的共表达增强了5HT1A受体的额外激活，而III型腺苷酸环化酶的共表达则没有增强，并且可能通过G蛋白的β - γ亚基进行。在注射大脑皮层mRNA的卵母细胞中，检测系统对血管活性肠肽和垂体腺苷酸环化酶激活多肽的反应也证明了该检测系统的敏感性。
The cystic fibrosis transmembrane conductance regulator (CFTR), a Cl- channel activated by phosphorylation, was expressed in Xenopus oocytes along with various combinations of several other components of the cAMP signalling pathway. Activation of the coexpressed beta 2 adrenergic receptor increased cAMP and led to CFTR activation. The activation of CFTR (1) requires only short (15 s) exposure to isoproterenol, (2) occurs for agonist concentrations 100-1000 fold lower than those that produce cAMP increases detectable by a radioimmunoassay, (3) requires injection of only 5 pg of receptor cRNA per oocyte, and (4) can be increased further by coexpression of cRNA for adenylyl cyclase type II or III or for Gs alpha. In addition, CFTR activation and cAMP increases by beta 2 activation were enhanced by activation of the coexpressed 5HT1A receptor, which is thought to couple to Gi. The additional activation by the 5HT1A receptor was enhanced by coexpression of adenylyl cyclase type II but not with type III and may proceed via the beta gamma subunits of a G protein. The sensitivity of the assay system is also demonstrated by responses to vasoactive intestinal peptide and to pituitary adenylate cyclase-activating polypeptide in oocytes injected with cerebral cortex mRNA.