B Montreuil

Université de Montréal, Montréal, Quebec, Canada

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Publications (5)12.6 Total impact

  • T A Reader, L Grondin, B Montreuil, K M Dewar
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    ABSTRACT: The binding characteristics of the novel benzazepine compound SCH23390 were studied using membrane preparations from rabbit cerebral cortex (CTX) and neostriatum (CPU; caudate putamen). The association kinetics of [3H]SCH23390 to membranes from CTX and CPU were rapid, while the dissociation kinetics were extremely slow and only around 40-60% of the binding was displaced two hours after the addition of either S(+)-butaclamol or 30 volumes of buffer. The saturation curves revealed that [3H]SCH23390 bound with high affinity in both tissues, with densities of 133 fmol/mg protein for CTX (Kd 25 degrees C = 0.31 nM) and 664 fmol/mg protein for CPU (Kd = 0.13 nM). the specificity of binding to the cortical D1 receptor was verified in competition experiments with a variety of dopaminergic agents. The rank order of potency of these compounds was consistent with the pharmacology of the dopaminergic D1 site. All competition curves were better fitted to a one-site model with Hill coefficients around one, indicating that [3H]SCH23390 was binding to a single cortical site. The stereoselectivity of the cortical [3H]SCH23390 binding site could be demonstrated by the use of enantiomer pairs of dopaminergic drugs. This study provides compelling evidence that [3H]SCH23390 binds to dopamine D1 receptors in the neostriatum and cerebral cortex of the rabbit.
    Archiv für Experimentelle Pathologie und Pharmakologie 01/1990; 340(6):617-25. · 2.15 Impact Factor
  • K M Dewar, B Montreuil, L Grondin, T A Reader
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    ABSTRACT: The binding properties of the substituted benzamide raclopride to dopamine D2 receptors were studied with membrane preparations from rat and rabbit neostriatum. An analysis of the association kinetics suggested a single binding site but the data from the dissociation experiments were better described by a two-site model. Examination of saturation curves at equilibrium revealed a single class of binding sites in the neostriatum from both species (rat: maximum binding capacity (Bmax) = 247 fmol/mg of protein; rabbit: Bmax = 337 fmol/mg of protein). In cortical regions known to possess a distinct dopaminergic innervation (piriform-entorhinal areas and cingulate cortex) the Bmax values ranged between 9 and 22 fmol/mg of protein. [3H]Raclopride binding sites (less than 12 fmol/mg of protein) were also detectable in the dorsal and ventral hippocampus as well as in the somatosensory and visual cortices. The selectivity in the neostriatum was examined by competition experiments with dopaminergic drugs. The rank of potency of agonists and antagonists to displace [3H]raclopride binding revealed its selectivity for the dopamine D2 receptor and was essentially the same for both species. Antagonist competition curves could be fitted to a single site but inhibition by agonists was better described assuming a two-site model. The stereospecificity of binding was demonstrated by the use of the enantiomer pairs. These results validate the utilization of the novel benzamide [3H]raclopride as a selective marker of dopamine D2 receptors.
    Journal of Pharmacology and Experimental Therapeutics 09/1989; 250(2):696-706. · 3.89 Impact Factor
  • E Gottberg, L Diop, B Montreuil, T A Reader
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    ABSTRACT: The effects of sodium, lithium, and magnesium on the in vitro binding properties of the D1 antagonist [3H]SCH23390 were examined with membrane preparations from rat neostriatum (CPU; caudate-putamen) and cerebral cortex (CTX). The saturation binding isotherms for both tissues performed in the presence of 120 mM of either Na+ or Li+ revealed an increase in the affinity, as compared to that observed when the incubation buffer was composed of Tris-Cl 50 mM with MgCl2 1 mM alone. For the CPU there were no changes in the maximum binding capacity (Bmax) in the different buffers used. In the case of the CTX, there was a loss of [3H]SCH23390 binding sites when either Na+ or Li+ 120 mM were added to the incubations, suggesting a lack of selectivity of this ligand in the absence of group IA cations. The agonist state of the [3H]SCH23390 binding site was studied in competition experiments with dopamine. The highest agonist affinity was obtained in 50 mM Tris-Cl buffer with 1 mM MgCl2 while the addition of 120 mM of either Na+ or Li+ caused a 3- to 5-fold decrease in the potency of dopamine to compete with specific [3H]SCH23390 binding in both CPU and CTX. The presence of magnesium was essential for the competition experiments; i.e.: a concentration of 1 mM MgCl2 was optimum to obtain dopamine antagonism of ligand binding, while increasing Mg2+ to 2 or 5 mM did not appear to further improve the inhibitions. The results support both agonist and antagonist affinity shifts for the dopamine D1 receptor labeled with [3H]SCH23390.(ABSTRACT TRUNCATED AT 250 WORDS)
    Neurochemical Research 06/1989; 14(5):419-26. · 2.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The effects of sodium, lithium, and magnesium on the in vitro binding properties of the D1 antagonist [3H]SCH23390 were examined with membrane preparations from rat neostriatum (CPU; caudate-putamen) and cerebral cortex (CTX). The saturation binding isotherms for both tissues performed in the presence of 120 mM of either Na+ or Li+ revealed an increase in the affinity, as compared to that observed when the incubation buffer was composed of Tris-Cl 50 mM with MgCl2 1 mM alone. For the CPU there were no changes in the maximum binding capacity (B max) in the different buffers used. In the case of the CTX, there was a loss of [3H]SCH23390 binding sites when either Na+ or Li+ 120 mM were added to the incubations, suggesting a lack of selectivity of this ligand in the absence of group IA cations. The agonist state of the [3H]SCH23390 binding site was studied in competition experiments with dopamine. The highest agonist affinity was obtained in 50 mM Tris-Cl buffer with 1 mM MgCl2 while the addition of 120 mM of either Na+ or Li+ caused a 3- to 5-fold decrease in the potency of dopamine to compete with specific [3H]SCH23390 binding in both CPU and CTX. The presence of magnesium was essential for the competition experiments; i.e.: a concentration of 1 mM MgCl2 was optimum to obtain dopamine antagonism of ligand binding, while increasing Mg2+ to 2 or 5 mM did not appear to further improve the inhibitions. The results support both agonist and antagonist affinity shifts for the dopamine D1 receptor labeled with [3H]SCH23390. Receptor affinity studies should take into account that pharmacological specificity may vary with the incubation buffer utilized, especially when comparing binding data from different laboratories performed under varying ionic conditions.
    Neurochemical Research 04/1989; 14(5):419-426. · 2.13 Impact Factor
  • E Gottberg, B Montreuil, T A Reader
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    ABSTRACT: The interactions between lithium and cortical dopaminergic receptors were investigated using the iontophoretic technique to record and apply dopaminergic compounds, GABA, acetylcholine and LiCl on neurons in the primary visual cortex of the rat. The main responses to dopamine (DA) or to the D1 agonist (+/- )SKF38393 on spontaneously-active (SA) or visually-driven (VD) units was a prolonged decrease in firing and a reduction in the responsiveness to pulses of acetylcholine. The D1 antagonist SCH23390, applied iontophoretically or intravenously, blocked or attenuated the inhibitory responses to both DA and (+/- )SKF38393. The D2 agonist quinpirole (LY171555) either produced only slight excitations or had no effects on both VD and SA units. The concomitant application of lithium blocked the inhibitory responses to DA and to (+/- )SKF38393 but did not modify the responsiveness to LY171555. In addition, the DA- and (+/- )SKF38393-induced decreases in responsiveness to acetylcholine were also suppressed by lithium. These effects were on dopaminergic mechanisms, since the excitatory responses to acetylcholine alone as well as the inhibitions caused by GABA were unchanged by the application of lithium. These results imply that the modifications in sensitivity to dopaminergic agents induced by lithium are mediated by dopamine D1 receptors and are discussed in relation to adenylate-cyclase.
    Synapse 02/1988; 2(4):442-9. · 2.31 Impact Factor

Publication Stats

55 Citations
12.60 Total Impact Points

Institutions

  • 1989–1990
    • Université de Montréal
      • Department of Radiology, Radiation Oncology and Nuclear Medicine
      Montréal, Quebec, Canada
    • Central University of Venezuela
      • Facultad de Medicina
      Caracas, Distrito Capital, Venezuela
  • 1988–1989
    • Université du Québec à Montréal
      • Department of Sociology
      Montréal, Quebec, Canada