Influence of Uptake ₁ and Uptake ₂ on the Relationship between Diffusion and Metabolism of Noradrenaline in the Perfused Rabbit Ear Artery

Abstract

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 uptake₁During 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 uptake₂When 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.