Kinetic aspects of l-quinuclidinyl benzilate interaction with muscarinic receptor |
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| Affiliation: | 1. Section of Receptor Biology & Signaling, Dept. Physiology & Pharmacology, Karolinska Institutet, S17177 Stockholm, Sweden;2. Section on Molecular Signal Transduction Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 35A Convent Drive, MSC 3752, Bethesda, MD 20892-3752, USA;3. Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany;4. Science for Life Laboratory, Department of Neuroscience, Karolinska Institute, SE-171 77 Stockholm, Sweden;5. Science for Life Laboratory, KTH-Royal Institute of Technology, SE-17121 Stockholm, Sweden;6. Faculty of Science, Institute of Experimental Biology, Masaryk University, Brno, Czech Republic;1. Ecole Nationale Vétérinaire d''Alfort, Epidemiology of Animal Infectious Diseases Unit, French Agency for Food, Occupational Health & Safety (Anses), Université Paris-Est, 94700 Maisons-Alfort, France;2. Laboratorio Central de Sanidad Animal (LCSA), Brucellosis National Reference Laboratory, 18320 Santa Fe, Granada, Spain;3. Veterinary and Agrochemical Research Centre (CERVA-CODA), Brucellosis National Reference Laboratory, 1180 Brussels, Belgium;4. Paris-Est University/Anses, Animal Health Laboratory, EU/OIE/FAO Brucellosis Reference Laboratory, 94706 Maisons-Alfort, France;5. Agri-Food and Biosciences Institute (AFBI), Veterinary Sciences Division, Immunodiagnostic Branch, Brucellosis National Reference Laboratory, Belfast BT4 3SD, Northern-Ireland, UK;6. Veterinary Laboratory of Larisa, Brucellosis National Reference Laboratory, 41110 Larisa, Greece;7. Istituto Zooprofilattico Sperimentale dell''Abruzzo e del Molise, Brucellosis National Reference Laboratory, 64100 Teramo, Italy;8. Instituto Nacional de Investigação Agrária e Veterinária (INIAV), Animal Production Health Unit, Brucellosis National Reference Laboratory, 1500-311 Lisbon, Portugal |
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| Abstract: | l-Quinuclidinyl benzilate is undoubtedly the most widely used radioactive reporter ligand for studies on muscarinic receptor. In the present Commentary the kinetic aspects of the interaction of this ligand with muscarinic receptor are summarized. On the basis of these results a kinetic mechanism has been proposed involving consequential isomerization of the receptor-ligand complex and cooperative regulation of this process by the excess of the ligand. In addition, the data give evidence of at least two different types of binding sites on the receptor. Owing to the solubilization of the receptor protein there occur remarkable changes in its kinetic properties. The kinetic analysis points to inadequacy of the simple one-step equilibrium binding scheme for l-quinuclidinyl benzilate interaction with muscarinic receptor, which may explain the apparently contradictory data in the literature, such as the large scattering of the Kd values and the different regularities described in the case of the receptor-ligand complex dissociation reaction. That points to the conclusion that l-quinuclidinyl benzilate is an “inconvenient” ligand for receptor studies, which call for true equilibrium conditions of the system. |
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