[Inactivation of naloxone binding with opioid receptors in rat brain membranes]

Inactivation of naloxone binding to rat brain membrane-bound mu-opioid receptors (37 degrees C) was studied using the radioligand method. The rate inactivation constant (k(in) = 5.2 +/- 1.0 x 10(-3) min-1), the activation energy (Ea = 82.5 kJ/mol) and the change in the activation entropy (delta S = -14 kJ/K.mol) were determined. Incubation with unsaturated fatty acids (linoleic and arachidonic acids, 10(-7)-10(-4) M), cardiolipin (10(-5)-10(-4) M), phosphatidylinositol (10(-5)-10(-4) M), 2.6-ditretbutyl-4-exitoluene (10(-4) M), and argon produced a significant stabilizing effect on naloxone binding. The microviscosity changes in the ESR probe (2,2,6,6-tetramethyl-4-capryloyloxypiperidine-1-oxyl) environment and peroxidase oxidation of membrane lipids during incubation of rat brain membranes were investigated. It was suggested that the main reason for the decrease in the opioid receptor activity is the peroxidation of unsaturated acid lipids in the specific receptor environment and the reduction of the lipid viscosity.