Abnormal levels of 3':5'-cyclic AMP in isoproterenol-stimulated fibroblasts from patients with cystic fibrosis.
To determine if the abnormalities of exocrine secretion characteristic of cystic fibrosis could be investigated in vitro, I studied the synthesis of 3':5'-cyclic AMP after isoproterenol stimulation in skin fibroblasts derived from patients with cystic fibrosis and from normal individuals. Comparison of normal and cystic fibrosis cells showed that the latter had 2- to 5-fold greater levels of intracellular cyclic AMP after stimulation with isoproterenol. The difference between the strains was observed at every stage of the culture cycle and was specific to stimulation by beta-adrenergic agonists. It could not be accounted for by different dose- or time-response curves nor by leakage of cyclic AMP into the medium. The increased sensitivity to catecholamines may reflect an intrinsic genetic property of cystic fibrosis cells, and it may be feasible to use this system to study the biochemical basis of the genetic defect in cystic fibrosis.[1]References
- Abnormal levels of 3':5'-cyclic AMP in isoproterenol-stimulated fibroblasts from patients with cystic fibrosis. Buchwald, M. Proc. Natl. Acad. Sci. U.S.A. (1976) [Pubmed]
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