Further properties of stereospecific opiate binding sites in rat brain: on the nature of the sodium effect.

Addition of sodium salts has been reported to enhance stereospecific binding of opiate antagonists while reducing binding of agonists to rat brain homogenate. We have tested, in addition to sodium and potassium, a number of organic cations. Our results support the suggestion that the ability to enhace antagonist binding is not a general characteristic of cations or high ionic strength, but a property of sodium ions. We have shown that the increase in antagonist binding results from an enhancement of binding affinity and not from unmasking of new binding sites. The reduction in etorphine binding in the presence of sodium is due to a decrease in binding affinity. This decrease is largely accounted for by an acceleration in the dissociation rate, while the greater affinity of naltrexone binding appears to be due to an increase in rate of association. Our results are consistent with the hypothesis of a conformational change in opiate binding sites in the presence of sodium, transformed sites exhibiting greater affinity for antagonists and reduced affinity for agonists. Preheating of rat brain P2 fraction at 50 degrees C results in gradual inactivation of stereospecific binding, but an increase in naltrexone binding is consistently observed after heating at 50 degrees C for 2 to 3 minutes, even at optimal concentrations of sodium.