Neurotensin modulates the binding characteristics of dopamine D2 receptors in rat striatal membranes also following treatment with toluene

G. VON EULER, K. FUXE, F. BENFENATI, T. HANSSON, L. F. AGNATI, Jan-Ake Gustafsson

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

The effects of neurotensin in vitro (1-100 nM) on the binding characteristics of [3H]N-propylnorapomorphine ([3H]NPA) were analysed in striatal membrane preparations of the adult male rat. Subsequently, it was investigated whether the modulatory effects of 10 nM neurotensin on [3H]NPA binding were altered by treatment with toluene in vivo (80 p.p.m., 3 days, 6 h day-1) and in vitro (19 μmol ml-1). Displacement of [3H]NPA binding by raclopride (IC50 about 15 nM) and SCH 23390 (without effect) indicated that [3H]NPA labelled only D2 dopamine receptors in the present study. Neurotensin was found to reduce the affinity of D2 receptors with a maximum response at 10 nM. At this concentration the K(D) value was increased by 30-40% without any consistent changes in the number of binding sites. The modulatory effect of neurotensin remained intact also following toluene treatment in vivo and in vitro, although at a higher K(D) range, since toluene alone increased the K(D) value of [3H]NPA binding by 40-50%. Thus, the mechanisms mediating the effects of neurotensin and toluene on the D2 receptor are likely to be different. When neurotensin and toluene treatments were combined, the K(D) values of [3H]NPA binding were about twice as high as in non-treated controls. These additive effects may lead to a severely decreased efficiency of dopamine D2-mediated neurotransmission in vivo.

Original languageEnglish (US)
Pages (from-to)443-448
Number of pages6
JournalActa Physiologica Scandinavica
Volume135
Issue number4
DOIs
StatePublished - Jan 1 1989

Keywords

  • dopamine receptors
  • membrane
  • neurotensin
  • rat
  • striatum
  • toluene.

ASJC Scopus subject areas

  • Physiology

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