EFFECT OF PARGYLINE ON BRAIN N-TELE-METHYLHISTAMINE IN PORTACAVAL-SHUNTED RATS - RELATION TO AMINE NEUROTRANSMITTERS

HPLC determination of histamine, serotonin, dopamine, and noradrenalin e in the brain tissue of rats with portocaval anastomoses (PCA) has re vealed a selective increase in histamine concentration. In the posteri or hypothalamus, the steady-state level of the amine metabolites showe d an inverse pattern; N-tele-methylhistamine (t-MeHA), as estimated by gas chromatography-mass spectrometry, was not changed significantly b y portocaval shunting, whereas 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid were more than doubled. Interestingly, the net incr ease in t-MeHA concentration in response to pargyline (80 mg/kg i.p.) was almost the same for PCA and sham-operated rats. This implies that the great enhancement of the histamine level in this area might be a c onsequence of the persistent stimulation of its synthesis and the unch anged activity of histaminergic neurons. In the rest of the brain, on the other hand, the steady-state level of t-MeHA was higher after PCA (3.8-fold), as were the levels of 5-HIAA and homovanillic acid. Surpri singly, t-MeHA remained unchanged after monoamine oxidase blockade. Of the pargyline-induced alterations in the concentrations of indoles an d catechols, the most pronounced were those in the serotonin level; se rotonin was elevated more than twofold in hypothalamus and more than 1 2-fold in the rest of the brain, with a concomitant 80% decrease in 5- HIAA. The dopamine and, to a much smaller extent, noradrenaline levels were also increased, and the levels of homovanillic acid and 3,4-dihy droxyphenylacetic acid fell below the detection limit. The study sugge sts that at least two different mechanisms operate in the brains of PC A rats to counteract the excessive synthesis of neuromediators, e.g., increased deposition and increased metabolism.