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Published 1993 | public
Journal Article

Receptors that couple to 2 classes of G proteins increase cAMP and activate CFTR expressed in Xenopus oocytes


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.

Additional Information

© 1993 Harwood Academic. (Received March 15, 1993; Revised May 15, 1993) We thank Dr.s M. Simon and Anna Aragay for advice and the gift of Gs cDNA, R. Reed for the gift of the adenyl cyclase type II cDNA, and Dr. B. Kobilka for the gift of the β2 receptor cDNA. We thank Drs. N. Dascal and C. Strader for comments on an earlier version of the manuscript. This work was supported by grants from the National Institutes of Health, the National Institute on Drug Abuse, the Silvio Conte Center for Neuroscience Research of the National Institute of Mental Health, the Cystic Fibrosis Foundation, the California Tobacco-Related Disease Program, the Wiersma Memorial Fund, and the Japanese Foundation for Clinical Pharmacology.

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October 25, 2023