REGULATION OF AROMATIC L-AMINO-ACID DECARBOXYLASE IN RAT STRIATAL SYNAPTOSOMES - EFFECTS OF DOPAMINE-RECEPTOR AGONISTS AND ANTAGONISTS

1 In. this study we investigated the effects of dopamine receptor agon ists and antagonists on rat striatal synaptosomal aromatic L-amino aci d decarboxylase (AADC) activity. 2 Tile results show that 10(-5)-10(-7 )M cis-flupenthixol increased the striatal synaptosomal AADC activity (by 25% to 57%) in a time-dependent manner. SCH 23390 and remoxipride alone had little or no effect on striatal synaptosomal AADC activity, but in combination they increased AADC activity by 20%, suggesting tha t the increases in striatal synaptosomal AADC activity occurred only a fter blockade of both dopamine D-1 and D-2 receptors. 3 Treatment with (+)-amphetamine and -2-(N-phenylethyl-N-propyl)amino-5-hydroxytetrali n hydrochloride ((+/-)-PPHT) produced a reduction of striatal synaptos omal AADC activity in a concentration- and time-dependent manner. SKF 38393 and (-)-quinpirole, however, exhibited no effect on striatal syn aptosomal AADC activity, suggesting that only the mixed dopamine recep tor agonists can reduce the AADC activity. Incubation with apomorphine at a concentration of 10(-4) M inhibited the AADC activity by 74% and this inhibition cannot be antagonized by SCH 23390, remoxipride or ci s-flupenthixol, suggesting that apomorphine-induced inhibition of stri atal synaptosomal AADC activity was not mediated by dopamine receptors . 4 cis-Flupenthixol can reverse the reduction of AADC activity induce d by (+)-amphetamine and (+/-)-PPHT. The inhibition of AADC activity e licited by (+/-)-PPHT also can be reversed by SCH 23390 and remoxiprid e. 5 The inhibition of striatal synaptosomal,AADC activity induced by (+/-)-PPHT is calcium-dependent and protein kinase C may play a role i n the regulation of striatal AADC activity. 6 These studies show that striatal synaptosomal AADC activity is regulated by dopamine receptors and indicate that in vitro dopamine D-1 and D-2 receptors have a syne rgistic effect in this regulation.