pH-Induced Alterations in Dopamine Synthesis Regulation in Rat Brain Striatal Synaptosomes

Abstract: Dopamine synthesis regulation as a function of pH has been examined in rat brain striatal synaptosomes. Synthesis stimulation produced by lowering the incubation pH from 7.2 to 6.2 is accompanied by a significant increase in apparent A'm for tyrosine and in apparent Vmax. While these kinetic alterations are similar to those produced by the depolarizing agent veratridine, it does not appear that synthesis is stimulated at pH 6.2 via synaptosomal depolarization since (1) synthesis stimulation still occurs at pH 6.2 in a calcium-free medium in contrast to the calcium-dependency of veratridine- induced stimulation and (2) tyrosine uptake is not inhibited by incubation at pH 6.2, but is markedly inhibited by veratridine. In order to study how the regulatory properties of synaptosomal preparations vary according to pH, the ability of synaptosomal dopamine synthesis to respond to various agents was tested between pH 7.2 and 6.2. The stimulatory effects of veratridine, amphetamine, phenylethylamine and dibutyryl cyclic AMP at pH 7.2 were significantly diminished at pH 6.2. In addition, incubation at pH 6.2 antagonized the veratridine-induced inhibition of tyrosine uptake, suggesting an interference with the depolarization process. The inhibitory effects of dopamine and tyramine at pH 7.2 were also antagonized at pH 6.2. In contrast to the effects of pH 6.2 buffer, incubation at pH 6.6 does not markedly alter responses to the various drugs. The results suggest that, although basal dopamine synthesis rates can be increased by lowering the pH, synaptosomal regulatory properties are significantly altered as the pH is lowered below 6.6.