URINARY EXCRETION OF NORADRENALINE AND ITS METABOLITES AT TEN-MINUTE INTERVALS AFTER INTRAVENOUS INJECTION OF dl-NORADRENALINE-2-C14*

Abstract

Normal young women were injected intravenously with 9.5 [mu]c of dl-noradrenaline-2-C14. The urine was collected at 10-minute intervals for 70 minutes; the urinary metabolites of noradrenaline (NA) were separated by column fractionation and their radioactivity measured by liquid scintillation. NA and the basic metabolites, normetadrenaline (NORMET) and an unknown, were eluted from Amberlite IRC-50. The acidic metabolites, NORMET conjugate (NORMET CONJ.), 3-methoxy-4-hydroxymandelic acid (MOMA), 3,4-dihydroxymandelic acid (DOMA), vanillic acid, protocatechuic acid, and sulfate of 3-methoxy-4-hydroxyphenylglycol, were eluted from Dowex-1-X2; other lesser metabolites, probably conjugates of the mandelic acids, conjugate of 3,4-dihydroxyphenylglycol, and several unknowns were also eluted from Dowex. The neutral metabolites appeared to be the glucuronide of NORMET and NA, 3-methoxy-4-hydroxyphenylglycol and 3,4-dihydroxyphenylglycol. Of the total radioactivity recovered in the urine 10 minutes after injection, 28 [plus or minus] 3% was labeled NA; this rapidly decreased but trace amounts were found for 6 to 18 hours. The NORMET and the basic unknown also declined. Concomitantly, the % of radioactivity rose in most of the acidic metabolites; MOMA rose from 13 [plus or minus] 8% in the first 10 minutes to 53 [plus or minus] 7% in the 30-40 minute period and the NORMET CONJ. rose from 5 [plus or minus] 2% to 14 [plus or minus] 3% in the 60-70 minute period; whereas the absolute quantities of MOMA rose, the NORMET CONJ. remained relatively the same. These results show that both oxidative deamination and O-methylation occur in the metabolism of noradrenaline; they occur simultaneously, but at different rates, depending upon the tissue involved.