Desensitization of guinea pig tracheal muscle preparation to beta-adrenergic stimulants by a preceding exposure to a high dose of catecholamines.
When a given concentration of a catecholamine was applied to guinea pig tracheal preparation contracted by 20 muM histamine or by 30 mM-K+-Tyrode's solution, constant relaxations were observed, if the relaxation was submaximal. When a high concentration of catecholamine, 200 times the ED50, was once applied, subsequent responses to beta-stimulants (ED80) was reduced by about 30-40%, in spite of repeated washings. The response was gradually recovered in 2 hr. Thus 45 muM epinephrine and 1 muM isoproterenol could cause desensitization to 0.65 muM EPINEPHRINE AND 0.03 muM isoproterenol, respectively. Epinephrine and isoproterenol could cause densensitization to isoprophenamine, a non-catechol beta-stimulant. Epinephrine did not affect the response to cyclic AMP, dibutyryl cyclic AMP, aminophylline and prostaglandin E1. This densensitization was not affected by phentolamine, normetanephrine nor by Ca2+ deprivation from the bathing solution. The mechanisms of the desensitization may relate to some step(s) between the receptor-drug interaction and cyclic AMP accumulation in the process of tracheal muscle relaxation induced by beta-stimulants.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000031:analogs & derivatives; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D009647:Normetanephrine / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D004983:Ethanolamines; D010627:Phenethylamines; D011458:Prostaglandins E; D009647:Normetanephrine; D000628:Aminophylline; C004350:clorprenaline; D003994:Bucladesine; D000242:Cyclic AMP; D007545:Isoproterenol; D002118:Calcium