My. Zhu et al., REGULATION OF AROMATIC L-AMINO-ACID DECARBOXYLASE IN RAT STRIATAL SYNAPTOSOMES - EFFECTS OF DOPAMINE-RECEPTOR AGONISTS AND ANTAGONISTS, British Journal of Pharmacology, 112(1), 1994, pp. 23-30
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.