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.