Dopamine D2 receptor stimulation inhibits inositol phosphate generating system in rat striatal slices

M. Pizzi, M. Da Prada, A. Valerio, M. Memo, P. F. Spano, W. E. Haefely

Research output: Contribution to journalArticlepeer-review

Abstract

Previous studies on the transduction mechanisms triggered by dopamine receptor stimulation have established that both D1 and D2 subtypes of dopamine receptors are linked to the adenylate cyclase system, the former in a stimulatory and the latter in an inhibitory manner. The present report provides the first evidence that stimulation of D2 receptors in rat brain tissue affects the turnover of polyphosphoinositides, a as revealed by changes of the content of inositol phosphates. We found that the basal level of [3H]inositol trisphosphate, [3H]inositol bisphosphate and [3H]inositol monophosphate decreased following the stimulation of the D2 receptor. The rank order of potency was quinpirole (IC50 5 nM) > lisuride (IC50 8 nM) > RU 24213 (IC50 50 nM) > dopamine (IC50 200 nM). In contrast, selective D1 receptor stimulation by fenoldopam did not alter the inositol monophosphate, inositol bisphosphate and inositol trisphosphate content. The quinpirole effect was prevented by selective D2 antagonists, such as domperidone and l-sulpiride (both 5 μM) while it was unaffected by the selective D1 antagonist SCH 23390 (100 nM) and by the pharmacologically inactive d-isomer of sulpiride. Our data indicate that the activation of striatal D2 receptors leads to the inhibition of inositol phosphate production.

Original languageEnglish
Pages (from-to)235-240
Number of pages6
JournalBrain Research
Volume456
Issue number2
DOIs
Publication statusPublished - Jul 26 1988

Keywords

  • Corpus striatum
  • D receptor
  • Dopamine
  • Inositol phosphate
  • Polyphosphoinositide
  • Quinpirole

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

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