Morris R G, Venning M G, de la Lande I S
Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia.
Blood Vessels. 1988;25(5):217-31. doi: 10.1159/000158734.
3H-metabolite effluxes from each surface of the perfused rabbit ear artery were measured during a 30-min period of application of 3H-(-)-noradrenaline (NA) to the intimal surface, the adventitial surface, and both surfaces simultaneously. The arteries were from reserpine-treated rabbits and were perfused in Ca-free medium containing prazosin to prevent the constrictor activity of NA. During intimal application, 3H-normetanephrine (NMN) was the principal metabolite. Effects of hydrocortisone, and of cocaine, indicated that (a) 3H-NMN was derived largely via uptake2, (b) 3H-3,4-dihydroxyphenylethylene glycol (DOPEG) was derived largely via uptake1, and (c) uptake2 limited access of the NA to sites of uptake1. During adventitial application, 3H-DOPEG was the principal metabolite. Effects of cocaine and hydrocortisone indicated that (a) 3H-DOPEG was derived largely via uptake1, (b) 3H-NMN was only partly derived via uptake2, and (c) uptake1 limited access of the NA to sites of uptake2. When 3H-NA entered both surfaces simultaneously, the effluxes of the deaminated catechols were identical to those prevailing during adventitial entry of the amine. In contrast, the effluxes of NMN corresponded more closely to the sum of those prevailing during entry via each surface separately. It is suggested that, in the perfused artery, regional differences in the diffusivity of NA between the adventitia and media are primarily responsible for the marked influence which the surface of entry exerts on exogenous NA metabolism.
在将3H-（-）-去甲肾上腺素（NA）分别施加于灌注兔耳动脉内膜表面、外膜表面以及同时施加于两侧表面的30分钟期间，测量了从灌注兔耳动脉各表面流出的3H代谢产物。这些动脉取自利血平处理过的兔子，并在含有哌唑嗪的无钙培养基中灌注，以防止NA的收缩活性。在内膜给药期间，3H-去甲变肾上腺素（NMN）是主要代谢产物。氢化可的松和可卡因的作用表明：（a）3H-NMN主要通过摄取2产生；（b）3H-3,4-二羟基苯乙二醇（DOPEG）主要通过摄取1产生；（c）摄取2限制了NA进入摄取1的位点。在外膜给药期间，3H-DOPEG是主要代谢产物。可卡因和氢化可的松的作用表明：（a）3H-DOPEG主要通过摄取1产生；（b）3H-NMN仅部分通过摄取2产生；（c）摄取1限制了NA进入摄取2的位点。当3H-NA同时进入两侧表面时，脱氨基儿茶酚的流出量与胺在外膜进入期间的流出量相同。相反，NMN的流出量更接近于分别通过每个表面进入期间的流出量之和。有人认为，在灌注动脉中，外膜和中膜之间NA扩散率的区域差异主要是导致给药表面对外源性NA代谢产生显著影响的原因。
