Springer Online Journal Archives 1860-2000
Summary In the dog kidney catecholamines are O-methylated before being secreted by the tubule (Hempel et al., 1973). Adrenaline was used in an investigation to determine whether or not O-methylation is a prerequisite for the tubular secretion of a catecholamine in the dog. In dogs (n=3) treated with the COMT inhibitor H22/54 [(±)-α-(3,4-dihydroxyphenyl)-n-valeramid] the excretion of 14C-(±)-adrenaline and the pattern 14C-adrenaline metabolites in urine were measured. 14C-adrenaline (9.2 μg per injection) was injected simultaneously with 3H-inulin into both renal arteries. Eigth injections of radioactive material were given to each animal. COMT was inhibited before the second 14C-adrenaline injection by infusion of H22/54 into the left renal artery in doses of 0.16, 0.72 and 3.2 mg/kg b.w., respectively. Without H22/54 the injected dose of 14C-adrenaline was excreted by the kidney within 12 min as followed: 22.2 ± 6.0% (n=6) as 14C-adrenaline, 21.8 ± 7.0% (n=7) as 14C-metanephrine, and 9.3 ± 2.2% (n=7) as deaminated or conjugated 14C-adrenaline metabolites. H22/54 reduced the excretion of 14C-metanephrine to 9–28.2% of the control value, whereas the 14C-adrenaline excretion was considerably increased, up to 200% of the control. It is concluded that the additional 14C-adrenaline observed in urine after COMT inhibition was secreted by the tubule. Thus, O-methylation seems not to be a prerequisite for tubular secretion of adrenaline in the dog.
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