Studies in vitro of amine uptake mechanisms in heart

Abstract

Amine uptake mechanisms of rabbit and rat heart slices were studied; l- and d-metaraminol, dl- α-methyl- m-tyramine, and l- and d- m-octopamine were accumulated by slices. The α-ethyl analog of metaraminol was taken up only slightly. Immunosympathectomy greatly inhibited metaraminol uptake, as did preheating slides, incubation in the cold, or presence of imipramine, cocaine, guanethidine, ouabain, or norepinephrine. Rabbit heart slices were much more sensitive to ouabain action than were rat heart slices. Reserpine or tetrabenazine had no effect on metaraminol uptake, but tetrabenazine or pretreatment with reserpine blocked m-octopamine accumulation. Treatment with a monamine oxidase (MAO) inhibitor reversed the effect of reserpine and allowed m-tyramine, normally not accumulated, to be taken up. Comparison of these results with findings in vivo provide evidence for the existence of two amine concentrating mechanisms: a relatively nonspecific mechanism in the neuronal membrane, which is blocked by a variety of drugs; and an intracellular mechanism of higher specificity which is blocked by reserpine or tetrabenazine. The results also emphasize the important role of MAO in regulation of amine stores and in the action of aminedepleting drugs.