Characterization of beta-1 and beta-2 adrenoceptors in guinea pig atrium: functional and receptor binding studies.
The selective beta-2 adrenoceptor agonist procaterol produced positive inotropic and chronotropic responses over a concentration range of 1 nM to 0.1 mM in spontaneously beating right atria and in three of seven electrically driven left atria. The pD2 values (right atria, 7.30; left atria, 7.18) were midway between its known affinities at beta-1 and beta-2 adrenoceptors and are evidence that positive inotropic and chronotropic responses involve a minor beta-2 adrenoceptor component. The pKB values for procaterol against (-)-isoproterenol in the right atria (5.59) and left atria (5.29) were consistent with its affinity for beta-1 adrenoceptors and suggest that these are responsible primarily for positive inotropic and chronotropic responses. Receptor binding studies in right atrial homogenates showed that [125I]cyanopindolol binding was saturable (KD = 36.2 pM, maximal density of binding sites = 49.2 fmol mg-1 protein) and stereoselective with respect to the isomers of propranolol. Competition binding curves for the beta-1 adrenoceptor antagonist CGP 20712A and beta-2 selective antagonist ICI 118,551 against [125I]cyanopindolol binding were resolved into two components using iterative curve fitting techniques. Binding sites with the characteristics of beta-1 and beta-2 adrenoceptors were present in the proportions of approximately 75 to 25%. These studies indicate either that the beta-1 adrenoceptor is coupled more efficiently to the positive inotropic and chronotropic response than the beta-2 adrenoceptor or that a proportion of the beta-2 adrenoceptors subserve other functions.
D000818:Animals; D004558:Electric Stimulation; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D017265:Procaterol; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013268:Stimulation, Chemical; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000378:metabolism
D004983:Ethanolamines; D007093:Imidazoles; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; C047975:cyanopindolol; D010869:Pindolol; C049763:CGP 20712A; D007545:Isoproterenol; D017265:Procaterol