Lymphocyte beta-adrenergic refractoriness induced by theophylline or metaproterenol in healthy and asthmatic subjects |
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Authors: | Philip J. Scarpace Michael R. Littner Donald P. Tashkin Itamar B. Abrass |
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Affiliation: | 1. Geriatric Research, Education and Clinical Center (GRECC) and Medical Service Sepulveda VA Medical Center Sepulveda, CA 91343, USA;2. Department of Medicine UCLA School of Medicine Los Angeles, CA 90024, USA |
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Abstract: | 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 concommitant 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. |
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