THE PHYSIOLOGICAL DISPOSITION OF H3-EPINEPHRINE AND ITS METABOLITE METANEPHRINE

Abstract

Methods for the estimation of H 3 -labeled epinephrine, metanephrine and their deaminated products are described. The concentrations of H 3 -epinephrine and its principal metabolite, H 3 -metanephrine, were determined in plasma and various tissues of cats after the intravenous administration of H 3 -epinephrine. H 3 -epinephrine was found to be taken up rapidly and selectively by heart, spleen and several glandular tissues. Only small amounts were found in muscle and negligible amounts in brain. Two hours after the intravenous administration significant concentrations were still present in all tissues examined. Two minutes after a rapid injection of H 3 - epinephrine the concentrations of H 3 -metanephrine were higher in most tissues than those of H 3 - epinephrine, indicating rapid O-methylation of the hormone during the period of its inactivation. Deamination during this time was negligible. H 3 -metanephrine was found to be present in relatively high concentration in liver, heart, kidney, spleen and lung. Only trace amounts were found in the brain. H 3 -metanephrine was retained by tissues but to a smaller extent than H 3 - epinephrine. The disappearance of H 3 -epinephrine from plasma after an intravenous injection has two phases: an initial rapid fall, reflecting diffusion into tissues and O-methylation, followed by a slower decline indicating a gradual release from binding sites and concurrent metabolism. Two minutes after the administration of H 3 -epinephrine, the plasma level of H 3 - metanephrine was slightly higher than and later paralleled that of the parent compound. The fate of H 3 -epinephrine was examined in the whole mouse after an intravenous injection. Within a few minutes more than half of H 3 - epinephrine was metabolized. Most of the epinephrine metabolized could be accounted for as metanephrine. The remainder of the epinephrine disappeared more slowly over a period of hours.