Elevated leukocyte cyclic AMP-phosphodiesterase in atopic disease: a possible mechanism for cyclic AMP-agonist hyporesponsiveness.
Previous studies have documented that leukocytes from atopic individuals show reduced cyclic AMP (cAMP) responsiveness to isoproterenol, histamine, and prostaglandin E1. We questioned whether this blunted response was due to rapid enzymic breakdown of cAMP. We measured cAMP-phosphodiesterase activity in mononuclear leukocytes of patients with atopic dermatitis and allergic rhinitis and noted consistent, significantly elevated levels. Kinetic studies showed differences in two of three leukocyte enzyme forms between normals and patients. Isolated lymphocytes from atopic dermatitis patients lacked a low Km phosphodiesterase form and showed an increase in the high Km, high-activity form seen in normal monocytes. The increased phosphodiesterase activity provides an explanation for the blunted cAMP responsiveness in atopic leukocytes and may reflect a basic biochemical characteristic relevant to abnormal immunocellular regulation in atopic disease.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000097:blood*; D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000527:Alprostadil; D000242:Cyclic AMP / Q000097:blood; D003876:Dermatitis, Atopic / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D007962:Leukocytes / Q000201:enzymology*; D008214:Lymphocytes / Q000201:enzymology; D009000:Monocytes / Q000201:enzymology; D011458:Prostaglandins E / Q000494:pharmacology; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology
D000319:Adrenergic beta-Antagonists; D011458:Prostaglandins E; D006632:Histamine; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000527:Alprostadil; D007545:Isoproterenol