Identification of multiple muscarinic binding site subtypes in cat and human cerebral vasculature. - Archive ouverte HAL Access content directly
Journal Articles Journal of Pharmacology and Experimental Therapeutics Year : 1992

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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Dates and versions

hal-02135327 , version 1 (21-05-2019)

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

Cite

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