Identification of multiple muscarinic binding site subtypes in cat and human cerebral vasculature.

Abstract : The binding characteristics of the nonselective muscarinic antagonist [3H]N-methyl scopolamine ([3H]NMS) have been studied in membrane fractions of cat and human cerebral blood vessels. A computer-fitting method was used to analyze the data obtained from association/dissociation, saturation and competition experiments. Specific binding of [3H]NMS to membrane preparations from cat and human pia-arachnoid vessels was found to be saturable (respective Bmax values of 98 +/- 15 and 67 +/- 7 fmol/mg protein) and of high affinity (KD values of 165 +/- 28 and 125 +/- 12 pM, respectively). Competition studies, in the presence of various well-characterized M1, M2 or M3 putative muscarinic antagonists, performed against the binding of [3H]NMS, revealed the heterogeneity of muscarinic binding sites in these vascular tissues. A population of M1 sites was clearly identified in both human and cat pial vessel membranes and accounted for approximately 40 (human) and 20% (cat) of the total population of cerebrovascular muscarinic binding sites labeled with [3H]NMS. Such observation was further supported by saturation studies of [3H]NMS binding performed under M1 blocking conditions (75 nM pirenzepine). Competition and saturation (in the presence of M2 antagonists) studies suggested the presence of M2 sites (approximately 35% of total sites) in cat pial vessels. However, under the same conditions, no M2 binding sites could be detected in human cerebrovascular membranes. A small population of M3 sites (approx. 20%) was found in both human and cat cerebrovascular membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
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https://hal-normandie-univ.archives-ouvertes.fr/hal-02135327
Contributeur : François Dauphin <>
Soumis le : mardi 21 mai 2019 - 11:15:54
Dernière modification le : lundi 26 août 2019 - 12:48:11

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  • HAL Id : hal-02135327, version 1
  • PUBMED : 1738116

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François Dauphin, Edith Hamel. Identification of multiple muscarinic binding site subtypes in cat and human cerebral vasculature.. Journal of Pharmacology and Experimental Therapeutics, American Society for Pharmacology and Experimental Therapeutics, 1992, 260 (2), pp.660-7. ⟨hal-02135327⟩

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