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 agonists and antagonists on rat striatal synaptosomal aromatic L-amino acid decarboxylase (AADC) activity. 2. The 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 that the increases in striatal synaptosomal AADC activity occurred only after blockade of both dopamine D1 and D2 receptors. 3. Treatment with (+)-amphetamine and (+/-)-2-(N-phenylethyl-N-propyl)amino-5- hydroxytetralin hydrochloride ((+/-)-PPHT) produced a reduction of striatal synaptosomal AADC activity in a concentration- and time-dependent manner. SKF 38393 and (-)-quinpirole, however, exhibited no effect on striatal synaptosomal AADC activity, suggesting that only the mixed dopamine receptor 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 cis-flupenthixol, suggesting that apomorphine-induced inhibition of striatal synaptosomal AADC activity was not mediated by dopamine receptors. 4. cis-Flupenthixol can reverse the reduction of AADC activity induced by (+)-amphetamine and (+/-)-PPHT. The inhibition of AADC activity elicited by (+/-)-PPHT also can be reversed by SCH 23390 and remoxipride. 5. The inhibition of striatal synaptosomal AADC activity induced by (+/-)-PPHT is calcium-dependent and protein kinase C may play a role in 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 DI and D2 receptors have a synergistic effect in this regulation.
Zhu
M Y
MY
Neuropsychiatric Research Unit, University of Saskatchewan, Saskatoon, Canada.
Juorio
A V
AV
Paterson
I A
IA
Boulton
A A
AA
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D004347:Drug Interactions; D066298:In Vitro Techniques; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology*
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011493:Protein Kinase C; D001142:Aromatic-L-Amino-Acid Decarboxylases; D002118:Calcium