Uptake, distribution and metabolism of isoprenaline in the dog saphenous vein

Abstract

Dog saphenous vein strips were incubated with 2 muM 3H-isoprenaline. After 2 and 8 min of incubation small cross sections were cut and prepared for light and ultrastructural autoradiography. In addition, the accumulation of 3H-isoprenaline (3H-ISO) in the tissue as well as the formation of 3-O-methylisoprenaline (3H-OMI) were determined by liquid scintillation counting. The density of silver grains was 6.5 times higher on smooth muscle than on connective tissue. It decreased from the intima to adventitia when determined in the 2 min specimens, suggesting the existence of a selective transport of isoprenaline through the endothelium of the vein. The preferential distribution into the juxta-intimal part of the media which was observed after the 2 min incubation period was abolished by cortexone. Silver grain density, especially over the smooth muscle, was markedly increased by U-0521 and decreased by cortexone. Simultaneous treatment with cortexone and U-0521 led to a marked accumulation of silver grains over neuronal tissue; this accumulation was prevented by cocaine. Strips incubated at 0 degrees C and without oxygen showed almost no grains. In control conditions the saphenous vein strips removed 1968 +/- 19 pmoles-g-1 during 8 min of incubation. 86.3% of that value corresponded to 3H-OMI formation. O-methylation of 3H-ISO was strongly inhibited by U-0521 and, in a lesser degree, by cortexone. The influence of U-0521 on inhibition of O-methylation of 3H-ISO was not modified by cortexone. We found a linear correlation between silver grain densities per unit area of the vein strips and the 3H-isoprenaline accumulation determined by liquid scintillation counting, indicating a clear correspondence between silver grains and 3H-isoprenaline.