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

Abstract

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 between 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 β-adrenergic stimulation. Speculation: The diminished cAMP response to β-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. © 1978 International Pediatric Research Foundation, Inc.