TY - JOUR T1 - Sino-Aortic Denervation Causes Right Atrial <em>Beta</em>Adrenoceptor Down-Regulation JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 677 LP - 685 VL - 280 IS - 2 AU - Angelina Zanesco AU - Regina C. Spadari-Bratfisch AU - Louis A. Barker Y1 - 1997/02/01 UR - http://jpet.aspetjournals.org/content/280/2/677.abstract N2 - Rat isolated right atria obtained 1 wk after sinoaortic denervation were less sensitive to the chronotropic actions of β-agonists than were tissues obtained from animals that underwent sham surgery or no surgery at all. The potencies, but not the maximal responses for two high efficacy agonists, norepinephrine and isoproterenol, were reduced about 3- to 4-fold. Sino-aortic denervation (SAD) caused about a 3-fold decrease in potency and about a 60% decrease in maximal response for a low efficacy agonist, prenalterol. The changes in the actions of these agonists occurred in the absence of any changes in the subtype ofbeta receptor mediating the chronotropic response. The results of analyses of the data for prenalterol showed that SAD caused a decrease in the operational efficacy of this agonist without any changes in its K D value forbeta-1 adrenoceptors. SAD had no effect on the responses of the tissue to blockade of uptake 1 and uptake 2, suggesting no compensatory changes in the removal processes caused the decreased potency. The results of radioligand binding assays showed that SAD caused a decrease in the maximal binding of125I-cyanopindolol without altering itsK D. Also, the results of competition binding assays confirmed the lack of effect of SAD on theK D for prenalterol. The SAD-induced changes in the actions of agonists acting at right atrial beta-1 receptors were caused by a down-regulation of beta-1 adrenoceptors, which probably occurred in response to SAD-induced increases in sympathetic tone. The American Society for Pharmacology and Experimental Therapeutics ER -