Possible Mechanisms of Binding of Gamma- Pyrones to the Opioid-Like Receptor
Pp. 62-95 (34)
Boris V. Krylov, Ilia V. Rogachevskii, Tatiana N. Shelykh and Vera B. Plakhova
Derivatives of gamma-pyrone show their remarkable ability to trigger the
novel mechanism of NaV1.8 channels modulation described in Chapter 1. Unlike
morphine, which activates both opioid and opioid-like receptors, comenic acid
specifically switches on the latter mechanism involving Na+,K+-ATPase as the signal
transducer. It is extremely important that not any gamma-pyrone derivative can
decrease the voltage sensitivity of NaV1.8 channels, though all molecules studied herein
share a rather similar chemical structure. A very productive approach which makes it
possible to elucidate the peculiarities of ligand-receptor binding on the molecular level
is combined application of quantum-chemical calculations and the patch-clamp
method. Below we present our findings that explain a totally unevident result of highly
selective binding of gamma-pyrone derivatives to the opioid-like receptor.
Understanding of this mechanism opens up opportunities for creation of a novel class
Ca2+ chelate complex, Gamma-pyrone derivatives, Limiting slope
procedure, NaV1.8 channels, Nociception, Opioid-like receptor, Patch-clamp
method, Quantum-chemical calculations.
I.P. Pavlov Institute of Physiology Russian Academy of Sciences St. Petersburg, Russia.