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. 