Lymphocyte beta-adrenergic refractoriness induced by theophylline or metaproterenol in healthy and asthmatic subjects.
Beta-adrenergic refractoriness was assessed in human lymphocytes following in vivo administration of the beta-adrenergic agonist, metaproterenol, the phosphodiesterase inhibitor, theophylline, or both concomitantly, to normal and asthmatic subjects. In normal subjects both beta-adrenergic receptor number and isoproterenol stimulated cAMP response decreases during therapy with metaproterenol (59 +/- 3; 51 +/- 16% of control, respectively), theophylline (76 +/- 6; 78 +/- 16), or concomitant metaproterenol and theophylline (47 +/- 4; 69 +/- 13). The asthmatic subjects were of two types; one type responding to metaproterenol or theophylline therapy by down regulation of receptor number to zero or near zero values, and a second group of asthmatics insensitive to down regulation of receptor number. The results suggest that the induction of the refractory state is different between asthmatics and non-asthmatics, and that there may be a role for cAMP in the development of beta-adrenergic refractoriness, in vivo.
D001249:Asthma / Q000097:blood* / Q000188:drug therapy; D000242:Cyclic AMP / Q000096:biosynthesis; D004082:Dihydroalprenolol / Q000378:metabolism; D004359:Drug Therapy, Combination; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009921:Metaproterenol / Q000008:administration & dosage / Q000494:pharmacology*; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013806:Theophylline / Q000008:administration & dosage / Q000494:pharmacology*
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D009921:Metaproterenol; D004082:Dihydroalprenolol; D013806:Theophylline; D000242:Cyclic AMP