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Streptomyces gabonae KY2234 was found to produce a new compound, MY336-a, which bound to beta-adrenergic receptor. The compound was isolated from the fermentation broth of KY2234. MY336-a showed a high affinity for the beta-receptor, labeled with [3H]dihydroalprenolol in the membrane fractions of rat heart (beta 1-adrenergic receptor) or lung (beta 2-adrenergic receptor), whereas the compound bound very weakly to alpha-adrenergic receptor, labeled with [3H]dihydroergokryptine in rat brain. the inhibition constants (Ki) of the compound were 0.73 and 0.14 microM for the beta-receptors of heart and lung, respectively. 5'-Guanylylimidodiphosphate (Gpp(NH)p) did not alter the affinity of the beta-receptors for MY336-a. In isolated guinea-pig atria, MY336-a produced an inhibition of the positive chronotropic and inotropic effects of isoproterenol. MY336-a also antagonized the relaxation of tone induced by isoproterenol in isolated guinea-pig trachea. No partial agonistic activity was detected in MY336-a in the isolated atria and trachea. In anaesthetized dogs, MY336-a (1 mg/kg, iv) exerted negative inotropic action (left ventricular dp/dt max, -32.6%).

MY336-a, a novel .BETA.-adrenergic receptor antagonist produced by Streptomyces gabonae.