Some effects of caffeine and aminophylline on the turnover of catecholamines in the brain

Abstract

The effect of caffeine and aminophylline on the turnover of noradrenaline and dopamine in the mouse brain was studied by two different methods: estimation of the rate of disappearance of the transmitter after inhibition of synthesis and measurement of the accumulation of [3H]noradrenaline (3H-NA) and [3H]dopamine (3H-DA) after administration of [3H]tyrosine. After inhibition of the tyrosine hydroxylase the xanthines had little or no effect on the disappearance of both catecholamines. After inhibition of dopamine β-hydroxylase, both xanthines increased the rate of disappearance of noradrenaline. When given in sufficiently large doses both xanthines increased the yield of 3H-NA and 3H-DA from [3H]tyrosine. Pretreatment with a monoamine oxidase inhibitor caused a decrease in the yield of the tritiated catecholamines, which could be counteracted by the xanthines. Stimulation of the noradrenaline receptors by clonidine appeared to cause a decrease in the yield of 3H-NA and an increase in the amount of 3H-DA formed from [3H]tyrosine. Conversely, stimulation of the dopamine receptors by apomorphine caused a decrease in the yield of 3H-DA and an increase in that of 3H-NA. Also, in caffeine-treated animals, clonidine and apomorphine decreased the yield of 3H-NA and 3H-DA respectively. However clonidine could not increase 3H-DA concentrations, nor apomorphine the 3H-NA concentrations more than did caffeine alone. Thus, caffeine and aminophylline appear to increase the rate of turnover of both catecholamines in the brain.