Response of the atrial pacemaker to dobutamine.
The action of dobutamine, (+/-)-4- [2- [[3-(p-hydroxyphenyl)-1-methylpropyl]amino]ethyl] pyrocatechol hydrochloride was studied on the pacemaker of the isolated rat atria. The dose-chronotropic response curve showed a typical bell-dome shape of the sympathomimetic amines. Reserpinization of the animals did not change the curve of the agonist. Cocaine (6.7 microgram/ml) induced a decrease of the sensitivity of the rat atria pacemaker for dobutamine (p less than 0.001). Propranolol (3 X 10(-8) and 10(-7) M) provoked a shift to the right of the dose-response curve for dobutamine. Also, the last concentration of the antagonist depressed the maxima (p less than 0.01). Phentolamine failed to prove a possible alpha-adrenergic action of the drug on the pacemaker. The response to dobutamine was not affected when monoaminoxidase was inhibited by pretreatment with pargyline, or when catechol-O-methyltransferase was inhibited by exposure to U-0521 (3,4 dihydroxy-alpha-methylpropiophenone). These results indicate that dobutamine: a) is a beta-adrenergic agent, b) is not a good substrate of MAO, c) is a direct-acting sympathomimetic amine.
D000319:Adrenergic beta-Antagonists; D000818:Animals; D065098:Catechol O-Methyltransferase Inhibitors; D002395:Catecholamines / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006325:Heart Atria / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects; D008297:Male; D008996:Monoamine Oxidase Inhibitors; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D011941:Receptors, Adrenergic / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013566:Sympathomimetics / Q000037:antagonists & inhibitors
D000319:Adrenergic beta-Antagonists; D065098:Catechol O-Methyltransferase Inhibitors; D002395:Catecholamines; D008996:Monoamine Oxidase Inhibitors; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D013566:Sympathomimetics; D004280:Dobutamine; D003042:Cocaine