Kinetics of in vivo binding of antagonist to muscarinic cholinergic receptor in the human heart studied by positron emission tomography |
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Authors: | A Syrota G Paillotin JM Davy MC Aumont |
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Institution: | 1. Service Hospitalier Frédéric Joliot and Service de Biophysique, Dept. de Biologie du C.E.A., 91406 Orsay, France |
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Abstract: | Positron Emission Tomography (PET) was used to analyse antagonist binding to human myocardial muscarinic cholinergic receptor. The methiodide salt of the muscarinic antagonist, quinuclidinyl benzilate (MQNB), was labeled with the positron emitter, Carbon-11, and injected intravenously to 8 normal subjects. 11C-MONB concentration was determined in the ventricular septum from 40 cross-sectional images acquired at the same transverse level over a period of 70 minutes. In 4 subjects, various amounts of unlabeled atropine were rapidly injected at 20 minutes to study whether atropine competitively inhibited MQNB.The kinetics of binding of 11C-MQNB were not the same and . The apparent dissociation rate of 11C-MQNB was much slower (by 1 to 2 orders of magnitude) than that observed with 3H-QNB. After atropine injection, 11C-MNQB dissociated from its binding sites at a rate that apparently depended on the amount of atropine present. 11C-MQNB kinetics were analysed with a mathematical model which assumes the existence of a boundary layer containing free ligand in the vicinity of the binding sites. The dissociation rate of the radioligand depends on the probability of its rebinding to a free receptor site. |
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