Decreased adenosine 3':5'-monophosphate response to isoproterenol in cystic fibrosis leukocytes.

Leukocyte preparations from cystic fibrosis (CF) patients produced markedly less adenosine 3':5'-monophosphate 
(cAMP) in response to isoproterenol than normal cells. Both stimulation ratio 
and net isoproterenol-stimulated accumulation of cAMP were significantly (P < 0.001) 
lower in mixed leukocyte preparations from 20 CF patients (29 trials) 
compared to 21 normal subjects (49 trials). There was no significant 
correlation of results with clinical score, and no differences in the 
CF group attributable to medications or presence of pancreatic insufficiency. CF 
heterozygotes had mean stimulation ratio and mean net isoproterenol-stimulated cAMP intermediate 
betweem normal and CF. There were no statistically significant differences among 
normal subjects, CF patients, and CF heterozygotes in basal cAMP or 
prostaglandin E1-stimulated cAMP. Purified mononuclear cells from five normal persons and 
seven CF homozygotes had the same basal and prostaglandin E1-stimulated cAMP, 
but isoproterenol-stimulated cAMP was markedly depressed (P < 0.01) in the 
CF cells. Granulocytes from six normal persons and nine CF patients 
also had the same basal and prostaglandin E1-stimulated cAMP, but isoproterenol-stimulated 
cAMP was decreased (P < 0.05) in the CF samples. These 
results clearly demonstrate a difference between normal and CF leukocytes in 
cAMP response to beta-adrenergic stimulation. The diminised cAMP response to beta-adrenergic 
stimulation in CF is probably related to the presence of a 
CF gene, and may interact with other genetic abnormalities to produce 
the clinical syndrome of CF. 