Relevance of second messengers in cystic fibrosis.

Water, electrolyte and macromolecular secretion, which is affected in cystic fibrosis, is 
regulated by neurotransmitters of the autonomic nervous system stimulating the cells 
by binding to alpha-adrenergic, beta-adrenergic and cholinergic receptors. Therefore, a genetic 
disturbance in cyclic 3'5'-adenosine monophosphate (c-AMP) response could eventually explain some 
of the manifold expressions of labile biochemical changes observed in CF, 
specially in tissue culture. We further characterized beta-receptors in cultured fibroblasts 
of CF patients and normal controls and investigated isoproterenol and prostaglandin 
E1-mediated c-AMP response using defined culture conditions. No significant difference was 
found between the two phenotypes on basal c-AMP values. With the 
exception of one cell line, CF strains had 25 to 180% 
increased c-AMP content. This difference is highly significant (p < 0.0025). 
This statistically significant difference in response can neither be attributed to 
differences in dose- or time-response curves nor to differential c-AMP escape 
into culture medium. Since CF cells synthesize more c-AMP than controls 
only in response to isoproterenol but not to prostaglandin E1, the 
alteration which might be responsible for the observed phenomenon is probably 
located proximal of the adenylate cyclase at the cells border between 
intra- and extracellular space. 