Denervation accelerates the reappearance of neostriatal D-2 receptors after irreversible receptor blockade

Kim A. Neve, Steve Loeschen, John F. Marshall

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

The effect of denervation on the turnover of striatal dopaminergic D-2 receptors was examined by determining the rate of receptor reappearance in vivo after administration of the irreversible receptor antagonist, N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) to rats that received prior unilateral intracerebral injection of 6-hydroxydopamine (6-OHDA). Initial experiments confirmed that EEDQ (10 mg/kg i.p.) induces a severe, prolonged blockade of D-2 receptors. Recovery of [3H]spiroperidol binding occurred at a rate of approximately 9% of control binding per day. 6-OHDA injection into the ascending dopaminergic projection 3 or 5 days prior to EEDQ administration revealed that denervation had no effect on the rate of D-2 receptor recovery during the first post-operative week. By 4-5 weeks postoperatively, however, denervation enhanced the rate of recovery of [3H]spiroperidol binding. These results are consistent with our finding that, when homogenized tissue preparations are used, steady-state receptor density does not change within the first postoperative week but increases by 3-4 weeks after the injury. Saturation analysis determined that both EEDQ and denervation altered the density of binding sites, whereas neither treatment significantly affected the affinity of the receptor for [3H]spiroperidol. By 4-5 weeks postoperatively, the receptor degradation rate constant in the denervated striatum (0.0054/h) was equal to that in the intact striatum (0.0052/h). Thus, only the receptor reappearance rate was elevated in the denervated striatum (3.8 fmol/mg protein/h) relative to the intact striatum (2.8 fmol/mg protein/h).

Original languageEnglish (US)
Pages (from-to)225-231
Number of pages7
JournalBrain research
Volume329
Issue number1-2
DOIs
StatePublished - Mar 11 1985

Keywords

  • [H]spiroperidol
  • denervation
  • dopamine D-2 receptor
  • receptor proliferation

ASJC Scopus subject areas

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

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