Summers R J, Molnaar P, Russell F, Elnatan J, Jones C R, Buxton B F, Chang V, Hambley J
Department of Pharmacology, University of Melbourne, Parkville, Australia.
Eur Heart J. 1989 Jun;10 Suppl B:11-21. doi: 10.1093/eurheartj/10.suppl_b.11.
Quantitative autoradiography was used to determine the location and density of beta 1- and beta 2-adrenoceptors in the right atrium (RA), left ventricular free wall (LVFW), right ventricular free wall (RVFW), interventricular septum (IVS), right atrium from an area near the atrioventricular node (RAAV) and cardiac nerves (N) taken from a patient with end-stage cardiac failure. The densities of beta-adrenoceptors detected by the non-selective beta-adrenoceptor antagonist radioligand (-)-[125I] cyanopindolol (50pM) were 4.93 (N), 10.6 (RVFW), 12.2 (RA), 12.4 (IVS), 15.8 (LVFW) and 18.7 fmol (mg protein)-1 (RAAV). The proportion of beta 2-adrenoceptors ranged from 19.5% (RAAV) to 95% (N). RA taken from patients with ischaemic heart disease had a higher density of beta-adrenoceptors (29.3 fmol (mg protein)-1). The results suggest that both beta 1- and beta 2-adrenoceptors are down-regulated in patients with end-stage cardiac failure. Positive inotropic responses were established to (-)-isoprenaline, RO363 (beta 1-selective), procaterol (beta 2-selective) and dopexamine in the absence or presence of the antagonist CGP 20712A (beta 1-selective) or ICI 118,551 (beta 2-selective) in electrically driven human right atrial appendage strips. RO363 and procaterol were nearly full agonists in this preparation and produced their responses through activation of beta 1- or beta 2-adrenoceptors, while dopexamine was a partial agonist which produced its inotropic responses through activation of both receptor subtypes. These studies demonstrate the presence and location of beta 1- and beta 2-adrenoceptors in the human heart.
采用定量放射自显影法测定了一名终末期心力衰竭患者右心房（RA）、左心室游离壁（LVFW）、右心室游离壁（RVFW）、室间隔（IVS）、房室结附近区域的右心房（RAAV）以及心脏神经（N）中β1和β2肾上腺素能受体的位置和密度。用非选择性β肾上腺素能受体拮抗剂放射性配体（-）-[125I]氰吲哚洛尔（50pM）检测到的β肾上腺素能受体密度分别为：4.93（N）、10.6（RVFW）、12.2（RA）、12.4（IVS）、15.8（LVFW）和18.7飞摩尔/（毫克蛋白）-1（RAAV）。β2肾上腺素能受体的比例在19.5%（RAAV）至95%（N）之间。取自缺血性心脏病患者的RA具有更高的β肾上腺素能受体密度（29.3飞摩尔/（毫克蛋白）-1）。结果表明，终末期心力衰竭患者的β1和β2肾上腺素能受体均下调。在电驱动的人右心耳条带中，在不存在或存在拮抗剂CGP 20712A（β1选择性）或ICI 118,551（β2选择性）的情况下，对（-）-异丙肾上腺素、RO363（β1选择性）、丙卡特罗（β2选择性）和多培沙明建立了正性肌力反应。RO363和丙卡特罗在该制剂中几乎是完全激动剂，通过激活β1或β2肾上腺素能受体产生反应，而多培沙明是一种部分激动剂，通过激活两种受体亚型产生正性肌力反应。这些研究证实了人心脏中β1和β2肾上腺素能受体的存在及其位置。
