Effect of beta adrenergic agonist, prostaglandins, and cortisol on lymphocyte levels of cyclic adenosine monophosphate and glycogen: abnormal lymphocytic metabolism in asthma.
Decreased beta adrenergic regulation of cyclic adenosine monophosphate (cAMP) in lymphocytes has been described in asthma. We investigated adrenergic stimulation of glycogenolysis and responses to prostaglandin E1 (PGE1). Lymphocytes from 24 normal and 24 mild asthmatic subjects who had no drugs for at least 2 weeks were separated on Ficoll-hypaque and incubated in medium 199 with Hepes buffer. Beta adrenergic stimulation of cAMP and glycogenolysis was reduced in the asthmatics (p less than 0.05). PGE produced less of a rise in cAMP in asthmatics than in normals, but the difference was not significant (p greater than 0.05) and glycogenolysis was normal. Cortisol added in vitro potentiates the effect of isoproterenol and PGE1--but in the presence of cortisol the response of the asthmatic cells to isoproterenol is still lower than that of normal cells. This observation would support that "beta adrenergic blockade" is the major defect of asthmatic cells. The conclusion is further supported by the observation that the degree of the blockade is associated with a pathologic condition.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D001249:Asthma / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004359:Drug Therapy, Combination; D004837:Epinephrine / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008214:Lymphocytes / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D011458:Prostaglandins E; D010656:Phenylephrine; D006003:Glycogen; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol; D006854:Hydrocortisone; D004837:Epinephrine; D010646:Phentolamine