Tachyphylaxis to beta-adrenoceptor agonists in human bronchial smooth muscle: studies in vitro.
In studies on human isolated peripheral airway smooth muscle; 1 A concentration dependent beta-adrenoceptor tachyphylaxis was observed to isoprenaline. 2 Cross desensitization to other beta-adrenoceptor agonists was demonstrated. 3 The desensitization was reversible with time. Hydrocortisone appeared to accelerate the recovery from the desensitized state. Low concentration isoprenaline (10(-9) mol l-1) prevented recovery whereas cyclohexamide 1.8 x 10(-4) mol l-1 had no noticeable effect on recovery. Continued occupancy of the receptor appears to prevent recovery. The recovery from the desensitized state does not apparently require synthesis of new proteins. 4 Bronchial wall cyclic AMP response to isoprenaline was attenuated after isoprenaline induced desensitization whereas total phosphodiesterase activity of bronchial wall was not altered by desensitization. Thus by exclusion the adenylate cyclase receptor complex may be altered in human peripheral airway smooth muscle beta-adrenoceptor tachyphylaxis.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000403:Airway Resistance / Q000187:drug effects*; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D004347:Drug Interactions; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D013618:Tachyphylaxis
D000318:Adrenergic beta-Agonists; D000242:Cyclic AMP; D007545:Isoproterenol