MY336-a, a novel beta-adrenergic receptor antagonist produced by Streptomyces gabonae.
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%).
Kase
H
H
Fujita
H
H
Nakamura
J
J
Hashizume
K
K
Goto
J
J
Kubo
K
K
Shuto
K
K
D000319:Adrenergic beta-Antagonists / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004082:Dihydroalprenolol / Q000378:metabolism; D004285:Dogs; D004347:Drug Interactions; D006168:Guinea Pigs; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D007546:Isoquinolines / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D044005:Tetrahydroisoquinolines; D014316:Tritium
D000319:Adrenergic beta-Antagonists; D007546:Isoquinolines; D011943:Receptors, Adrenergic, beta; D044005:Tetrahydroisoquinolines; D014316:Tritium; D004082:Dihydroalprenolol; C048654:MY 336-a; D007545:Isoproterenol