Distribution and effects of intestinally administered [ 14C]-tyramine in cats, modified by monoamine oxidase inhibitors

Abstract

Due to the increasing importance of the amine in psychiatric research, [ 14C]-tyramine was instilled intraduodenally (i.d.), into the colon or infused into the portal vein of chloralosed or spinal cats in order further to investigate its metabolism, distribution and interactions. Tyramine and p-hydroxyphenylacetic acid ( pHPA) accounted for 83% of the radioactivity recovered in blood, the remainder being octopamine, tyramine sulphate, methyltyramine and tyrosol, Progressively greater portal venous (PV), cranial mesenteric arterial (CMA) and PV-CMA concentrations of tyramine and pHPA were observed with an increase in the amount of tyramine instilled i.d.; pHPA preponderated over tyramine in portal venous and arterial blood. Tyramine and pHPA also appeared in portal and arterial blood after installation of [ 14C]-tyramine into the colon. When histamine (5 μmol/kg) was combined with tyramine i.d., 1.7 μmol/kg, tyramine and pHPA were significantly increased in portal venous and arterial blood, in liver and in distal intestine. Arterial tyramine concentrations were increased 7- to 46-fold by the non-selective MAO inhibitors tested following tyramine, 1.7 μmol/kg i.d.; arterial pHPA was reduced despite the elevated tyramine. The proportion of octopamine, tyramine sulphate, methyltyramine and tyrosol was not increased by mebanazine over the duration of experiments. Clorgyline but not deprenyl elevated portal venous and arterial tyramine. Sympathomimetic effects were obtained with infusion for 20 min of tyramine, 340 (nmol/kg)/min, into the portal vein (arterial tyramine concentration > 2.6 nmol/ml) but not with infusion of 85 or 170 (nmol/kg)/min (arterial tyramine concentration < 1.25 nmol/ml) either in control cats or those pretreated with clorgyline but were elicited in cats treated with mebanazine when arterial tyramine concentrations reached 3 nmol/ml. Sympathomimetic effects were elicited also by tyramine 8.5 μmol/kg i.d. after clorgyline, arterial mean tyramine concentration being 2.4 nmol/ml; tyramine, 17 μmol/kg i.d., in the absence of clorgyline failed to evoke sympathomimetic phenomena despite arterial mean tyramine concentration increasing to 2.2 nmol/ml. [ 14C]-Tyramine and pHPA were found in the liver, lungs, distal small intestine and kidney after tyramine instilled i.d. The amount of [ 14C]-tyramine and pHPA in the kidney of control cats was between 7- and 32-fold than in other tissues. With tyramine, 1.7 μmol/kg i.d., tyramine content of tissues was substantially increased by the non-selective MAO inhibitors and in the liver and small intestine by clorgyline but not by deprenyl. In vitro inhibition of MAO A was 80% with the non-selective MAO inhibitors, 70% with clorgyline and 30–45% with deprenyl; except for the liver, where deprenyl and the non-selective MAO inhibitors were effective, in vitro inhibition of MAO B was less satisfactory. In vitro inhibition of tyramine oxidation was 47% or more with all the MAO inhibitors, except in the distal small intestine.