Increased cyclic AMP levels and beta-adrenergic antagonist binding in cystic fibrosis fibroblasts.

The possibility of altered B-adrenergic receptors and/or adenyl cyclase activity in fibroblasts from patients with cystic fibrosis (CF) has been raised by several groups of investigators. Buchwald (1) reported a greater increase in CAMP’ after isoproterenol stimulation in CF than in normal fibroblasts and this was confirmed by Roscher et al. (2) for CF and normal fibroblasts in fresh medium. Furthermore, CF fibroblasts were shown to be more resistant to the cytotoxic effects of exogenous dibutyrl CAMP or isoproterenol than were normal fibroblasts (3). However, Buchwald and Mapelson (4) and Davis et al. (5) could not reproduce these differences in response to isoproterenol between CF and normal cultured skin fibroblasts. The CAMP response of fibroblasts to isoproterenol is known to be highly sensitive to time and cell density in culture (6) and the negative reports on differences between CF and normal fibroblasts (4,5) noted high day-to-day variability. We have studied the response to metaproterenol (a congener of isoproterenol) of pairs of CF and normal fibroblast strains compared blind on the same day and found greater responses in the CF strains. We have sought the basis for this difference by measuring B-adrenergic receptors and find increased binding capacity for a P-adrenergic antagonist.