Allosteric changes in opioid receptors induced by the electric footshock

The present electric shock (ES) schedule followed in these experiments produced different functional changes in opioid agonist- and antagonist-type receptors, depending on the type of receptor: The amount of [³H]-naloxone specific binding was increased by ES application, while the amount of [³H]-D-Ala², Met⁵-enkephalinamide ([³H]-DAMEA) specific binding was decreased. In order to elucidate the mechanism of these changes in ES membrane, we investigated whether biochemical nature of ES membrane is different from the control membrane. In the competition experiments, 50% inhibitory concentration (IC₅₀) values of unlabeled naloxone against [³H]-naloxone specific binding in both control and ES membranes were equal, but the Hill coefficient of ES membrane was significantly different from that of control membrane. In addition, although the additions of sodium and lithium cations increased [³H]-naloxone specific binding, while they decreased [³H]-DAMEA specific binding in the control membrane, these effects of the cations were not shown in the ES membrane. In addition, the significant differences between control and ES membranes in the effects of guanosine-5'-triphosphate (GTP) and its stable analogue guanyl-5'-imidodiphosphate were not observed. These results suggest that the present ES schedule produces allosteric changes of opioid receptor in the rat brain, which attenuate the effect of sodium cation but not GTP.