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Canadian Journal of Anesthesia, Vol 15, 545-553, Copyright © 1968 by Canadian Anesthesiologists' Society

Nuclear Magnetic Resonance Studies of Junctional Transmitter-Receptor Interactions

G. KATO PH.D.1

1 Wellcome Department of Research in Anaesthesia, McGill University, Montreal

The technique of nuclear magnetic resonance spectroscopy was used to study the interaction between ACh and cholinesterase or muscle "receptor" protein. With a pure solution of ACh, the nuclear magnetic resonance occurs over a narrow region of magnetic field and therefore sharp absorption bands are observed. As molecular motion decreases, the absorption bands are broadened. From the broadening of the observed lines it is possible to deduce the degree of binding.

By extraction with phosphate buffer, a protein was isolated from skeletal muscle which binds acetylcholine. The NMR spectrum of a solution of AChCl in D2O consists of three major peaks, the first of which is attributed to the four protons attached to the carbon skeleton, and the other two to the methyl groups on the quaternary nitrogen and the methyl groups of the acetate radical. Upon addition of "receptor" protein, a selective broadening of the ACh spectral peaks is observed. This binding between ACh and protein is transient and is prevented by d-tubocurarine. The transient nature of the ACh-receptor interaction is consistent with a physiological action of ACh at the receptor site. The interaction is a two-point stabilization of the ACh molecule and is independent of cholinesterase sites. Addition of ChE to ACh solutions also causes a marked broadening of the ACh spectral peaks. The broadening of the quaternary ammonium peak reaches a maximum after ten minutes and it then decays exponentially. The initial binding of the quaternary ammonium and acetate groups of ACh by ChE, as well as the enzymatic hydrolysis of ACh, is blocked by ChE inhibitors and by local anaesthetics. Volatile anaesthetics had little or no effect. With nembutal, the maximum binding rate between ACh and ChE was accelerated and there was a concomitant potentiation of the rate of hyrolysis of ACh.






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Copyright © 1968 by the Canadian Anesthesiologists' Society.