In vivo renal production and tubular secretion of tyramine.
Para-tyramine (p-TYM) is a predominant urinary amine in humans, rabbit, rat and dog, and its urinary excretion rate may reflect central nervous system pathophysiology. However, the source of urinary p-TYM is not known, nor have the mechanisms regulating its excretion been characterized. The present study, by using renal clearance techniques, examined the sources of urinary p-TYM and the mechanism of excretion in anesthetized rabbits. In all studies, the renal clearance of p-TYM was compared 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-TYM was 26.5 +/- 3.6 ng/min during the same period (P < .001 vs. delivery). In three separate series of experiments, either vehicle (n = 5) or a specific inhibitor of 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 arterial pressure, glomerular filtration rate, renal plasma flow and urine flow rate were unchanged in all studies. The renal clearances of p-TYM (Cp-TYM) and NE (CNE) were unchanged only after vehicle. After cyanine 863, Cp-TYM was decreased to 36% of control (P < .01), whereas CNE decreased to 21% of its base-line value (P < .01). After FMD Cp-TYM was reduced to 2% of control (P < .05), whereas CNE decreased by 44% (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
Van Huysse
J W
JW
Department of Medicine, Indiana University School of Medicine, Indianapolis.
Henry
D P
DP
Willis
L R
LR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D008750:Methyldopa / Q000031:analogs & derivatives / Q000494:pharmacology; D009638:Norepinephrine / Q000652:urine; D011806:Quinolinium Compounds / Q000494:pharmacology; D011817:Rabbits; D014439:Tyramine / Q000652:urine*; D010130:p-Aminohippuric Acid / Q000652:urine
D011806:Quinolinium Compounds; C016855:cyanine 863; D008750:Methyldopa; C019494:alpha-monofluoromethyldopa; D009638:Norepinephrine; D014439:Tyramine; D010130:p-Aminohippuric Acid