IN-VIVO RENAL PRODUCTION AND TUBULAR SECRETION OF TYRAMINE

Para-tyramine Go-NM) is a predominant urinary amine in humans, rabbit, rat and dog, and its urinary excretion rate may reflect central nervo us system pathophysiology. However, the source of urinary p-NM is not known, nor have the mechanisms regulating its excretion been character ized. The present study, by using renal clearance techniques, examined the sources of urinary p-TYM and the mechanism of excretion in anesth etized rabbits. In all studies, the renal clearance of p-TYM was compa red with that of norepinephrine (NE). Base-line delivery to the kidney of p-TYM in plasma was 8.6 +/- 1.6 ng/min (mean +/- S.E.M., n = 16), whereas the mean urinary excretion rate of p-PYM was 26.5 +/- 3.6 ng/m in during the same period (P < .001 vs, delivery). In three separate s eries of experiments, either vehicle (n = 5) or a specific inhibitor o f renal tubular organic cation secretion, cyanine 863 (6 mg/kg, n = 7) , or a specific inhibitor of aromatic-amino acid-decarboxylase, alpha- mono-fluoromethyldopa (FMD, 4 mg/kg, n = 5), were infused i.v.. Mean a rterial pressure, glomerular filtration rate, renal plasma flow and ur ine flow rate were unchanged in all studies. The renal clearances of p -TYM (C-p-TYM) and NE (C-NE) were unchanged only after vehicle. After cyanine 863, C-p-TYM was decreased to 36% of control (P<.01), whereas C-NE decreased to 21% of its base-line value (P<.01). After FMD C-p-TY M was reduced to 2% of control (P<.05), whereas C-NE decreased by 44% (P<.01). The plasma concentration of NE did not change after FMD, wher eas that of p-TYM was decreased (to 70% of control, P<.02). Inasmuch a s the base-line urinary output of p-TYM was 3.1 times greater than the delivery of p-TYM in plasma to the kidney, at least 76% of urinary p- TYM must have been produced in the kidney. Therefore, the urinary excr etion of p-TYM is unlikely to directly reflect central nervous system pathology, unless a defect in brain metabolism is accompanied by a sim ilar defect in the kidney. Both NE and p-TYM are secreted by renal tub ular organic cation transport, and nearly all of the urinary p-TYM is produced by aromatic-amino acid-decarboxylase.