Regulation of Aromatic l ‐Amino Acid Decarboxylase by Dopamine Receptors in the Rat Brainстатья из журнала
Аннотация: Abstract: Decarboxylation of phenylalanine by aromatic l ‐amino acid decarboxylase (AADC) is the rate‐limiting step in the synthesis of 2‐phenylethylamine (PE), a putative modulator of dopamine transmission. Because neuroleptics increase the rate of accumulation of striatal PE, these studies were performed to determine whether this effect may be mediated by a change in AADC activity. Administration of the D 1 antagonist SCH 23390 at doses of 0.01–1 mg/kg significantly increased rat striatal AADC activity in an in vitro assay (by 16–33%). Pimozide, a D 2 ‐receptor antagonist, when given at doses of 0.01–3 mg/kg, also increased AADC activity in the rat striatum (by 25–41%). In addition, pimozide at doses of 0.3 and 1 mg/kg increased AADC activity in the nucleus accumbens (by 33% and 45%) and at doses of 0.1, 0.3, and 1 mg/kg increased AADC activity in the olfactory tubercles (by 23%, 30%, and 28%, respectively). Analysis of the enzyme kinetics indicated that the V max increased with little change in the K m with l ‐3,4‐dihydroxyphenylalanine as substrate. The AADC activity in the striatum showed a time‐dependent response after the administration of SCH 23390 and pimozide: the activity was increased within 30 min and the increases lasted 2–4 h. Inhibition of protein synthesis by cycloheximide (10 mg/kg, 0.5 h) had no effect on the striatal AADC activity or on the increases in striatal AADC activity produced by pimozide or SCH 23390. The results indicate that the increases in AADC activity induced by dopamine‐receptor blockers are not due to de novo synthesis of the enzyme. These results show that AADC activity in the striatum is regulated by D 1 and D 2 receptors and that the activities in the nucleus accumbens and olfactory tubercles are regulated by D 2 receptors. The observation that dopamine‐receptor antagonists stimulate the synthesis of PE may be explained by the increase in AADC activity.
Год издания: 1992
Авторы: Meng‐Yang Zhu, A. V. Juorio, I.A. Paterson, A. A. Boulton
Издательство: Wiley
Источник: Journal of Neurochemistry
Ключевые слова: Polyamine Metabolism and Applications, Neurotransmitter Receptor Influence on Behavior, Amino Acid Enzymes and Metabolism
Другие ссылки: Journal of Neurochemistry (HTML)
PubMed (HTML)
PubMed (HTML)
Открытый доступ: closed
Том: 58
Выпуск: 2
Страницы: 636–641