PT - JOURNAL ARTICLE AU - MICHAEL J. PEACH AU - ANDREW T. CHIU TI - THE INFLUENCE OF ACIDOSIS ON THE CHRONOTROPIC EFFECTS OF TYRAMINE IN GUINEA-PIG ATRIA: RELATION TO TYRAMINE UPTAKE AND METABOLISM DP - 1972 Oct 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 73--79 VI - 183 IP - 1 4099 - http://jpet.aspetjournals.org/content/183/1/73.short 4100 - http://jpet.aspetjournals.org/content/183/1/73.full SO - J Pharmacol Exp Ther1972 Oct 01; 183 AB - It has been reported that acidosis depressed the chronotropic effects of tyramine. Spontaneously beating right guinea-pig atria were placed in 10 ml of Krebs-Henseleit solution at 35°C, pH 7.0 or 7.6 with oxygenation by 95% O2-5% CO2. After equilibration, chronotropic effects were obtained with tyramine at pH 7.6 or 7.0, isoproterenol at pH 7.6 or 7.0, tyramine + diethyldithiocarbamate, pH 7.6, tyramine + cocaine, pH 7.6, and tyramine + phenoxybenzamine, pH 7.6. Cocaine, phenoxybenzamine, diethyldithiocarbamate and acidosis were also studied for effects on the uptake and metabolism of 14C-tyramine. 14C-tyramine and its metabolites (14C-octopamine, 14C-p-hydroxyphenylacetic acid and 14C-p-hydroxymandelic acid) were isolated via thin-layer chromatography and quantified by liquid scintillation spectrometry. Cocaine and phenoxybenzamine blocked the chronotropic effects of tyramine and decreased atrial 14C-tyramine and the levels of all three metabolites of tyramine. Diethyldithiocarbamate, an inhibitor of dopamine-β-hydroxylase, potentiated chronotropic effects of tyramine and markedly decreased atrial levels of 14C-octopamine and 14C-p-hydroxymandelic acid. This agent also reduced 14C-tyramine levels but had no effect on 14C-p-hydroxyphenylacetic acid levels. Acidosis caused a decrease in the chronotropic effects of 14C-tyramine and markedly increased β-hydroxylated and deaminated metabolites of tyramine in the atria. The data suggest that acidosis alters the storage capacity or binding affinity for amines in the adrenergic neuron. © 1972, by The Williams & Wilkins Company