Kinetic aspects of l-quinuclidinyl benzilate interaction with muscarinic receptor.
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 K(d) 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.
Järv
J
J
Laboratory of Bioorganic Chemistry and Laboratory of Enzymology, Tartu State University, 202 400 Tartu, Estonian SSR, U.S.S.R.
Eller
M
M