[3H]WIN 35,428 [2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane] binding to rat brain membranes. Comparing dopamine cell body areas with nerve terminal regions

Biochem Pharmacol. 1996 Feb 23;51(4):563-6. doi: 10.1016/0006-2952(95)02208-2.

Abstract

Potential differences between somatodendritic acid and axonal dopamine transporters were examined by comparing the binding constants of [3H]WIN 35, 428 [2 beta-carbomethoxy- 3 beta-(4-fluorophenyl)tropane] binding to membranes prepared from the rat ventral mesencephalon, containing A9 and A10 dopamine cell bodies, and from the nucleus accumbens. Saturation analysis of [3H]WIN 35,428 binding, in the presence of compounds to occlude norepinephrine and serotonin transporters, was performed by both the "unlabeled" method (varying unlabeled ligand) and "labeled" method (varying radioligand). The density of binding was substantially lower in the ventral mesencephalon than in the nucleus accumbens, but the binding affinity was only slightly different. Likewise, the differences between the two regions in the inhibitory potency of cocaine and GBR 12909 [1-(2-di(4-fluorophenyl)-methoxy-ethyl)4-(3-phenylpropyl)piperazine] were not substantial. The results suggest that somatodendritic and axonal dopamine transporters in the ventral mesencephalon and nucleus accumbens are not very different as far as their binding domains for uptake blockers such as cocaine and GBR 12909 are concerned.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / metabolism*
  • Cell Membrane / metabolism
  • Cocaine / analogs & derivatives*
  • Cocaine / metabolism
  • Dopamine / metabolism*
  • Dopamine Uptake Inhibitors / metabolism*
  • Kinetics
  • Male
  • Mesencephalon / metabolism
  • Nerve Endings / metabolism*
  • Nucleus Accumbens / metabolism
  • Piperazines / metabolism
  • Radioligand Assay
  • Rats
  • Rats, Sprague-Dawley
  • Tritium

Substances

  • Dopamine Uptake Inhibitors
  • Piperazines
  • Tritium
  • (1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester
  • vanoxerine
  • Cocaine
  • Dopamine