Kobayashi Y, Ricci A, Rossodivita I, Amenta F
Sezione di Anatomia Umana, Istituto di Farmacologia, Università di Camerino, Italy.
Naunyn Schmiedebergs Arch Pharmacol. 1994 Jun;349(6):559-64. doi: 10.1007/BF01258459.
In the present study, the pharmacological characteristics and the anatomical localization of dopamine D2-like receptor sites in the extraparenchymal and in the intraparenchymal portion of the rabbit pulmonary artery were investigated using combined radioligand binding and light microscope autoradiography with [3H]-spiroperidol (spiperone) as a ligand. The ligand was bound to sections of the pulmonary artery in a manner consistent with the labelling of dopamine D2-like receptors with an equilibrium dissociation constant (Kd) of about 2.4 +/- 0.07 nmol/l and a maximum density of binding sites of 65 +/- 4.5 fmol/mg tissue. In contrast, binding experiments made with sections of rabbit lung did not allow the evaluation of specific binding. Light microscope autoradiography showed the development of specific silver grains within the tunica adventitia of extraparenchymal branches of rabbit pulmonary artery and of large and, to a lesser extent, of medium-sized intraparenchymal branches of the pulmonary artery. No silver grains were found within small branches of the pulmonary artery or of the pulmonary vein. Development of adventitial silver grains was inhibited by compounds active at dopamine receptors. The greater sensitivity to displacement by domperidone, haloperidol, (-)-sulpiride and bromocriptine than to displacement by N-propyl-norapomorphine, quinpirole or clozapine suggests that the [3H]-spiroperidol binding sites observed in extraparenchymal, large and medium-sized branches of the pulmonary artery belong, probably, to the dopamine D2 receptor subtype. The possible pre-junctional localization of these sites is discussed.
在本研究中,使用[³H] - 螺哌啶醇(舒必利)作为配体,通过放射性配体结合与光学显微镜放射自显影相结合的方法,研究了兔肺动脉实质外和实质内部分多巴胺D2样受体位点的药理学特性和解剖定位。配体与肺动脉切片的结合方式与多巴胺D2样受体的标记一致,其平衡解离常数(Kd)约为2.4±0.07 nmol/L,结合位点的最大密度为65±4.5 fmol/mg组织。相比之下,用兔肺切片进行的结合实验无法评估特异性结合。光学显微镜放射自显影显示,在兔肺动脉实质外分支的外膜以及肺动脉大的和较小程度的中等大小实质内分支中出现了特异性银颗粒。在肺动脉或肺静脉的小分支中未发现银颗粒。外膜银颗粒的形成受到多巴胺受体活性化合物的抑制。与N - 丙基 - 去甲阿扑吗啡、喹吡罗或氯氮平相比,多潘立酮、氟哌啶醇、( - ) - 舒必利和溴隐亭对其置换的敏感性更高,这表明在肺动脉实质外、大的和中等大小分支中观察到的[³H] - 螺哌啶醇结合位点可能属于多巴胺D2受体亚型。本文还讨论了这些位点可能的节前定位。