An analysis of binding at the opioid receptor based upon an agonist/antagonist two-state model

Experimental binding data for a number of opioid agonists and antagonists in homogenate of rat brain membranes at 0 degrees have been analyzed in terms of the two-state Snyder-Pert receptor model. By means of iterative nonlinear regression techniques, it was possible to evaluate the affinity constants characterizing the binding of each drug at the agonist and antagonist states of the receptor. In addition, the role of Na+ in determining the state of the receptor has been described quantitatively. The findings of this study are discussed in terms of the index, fr, which provides a theoretical measure of the fraction of receptors existing in the agonists state. The graph of fr as a function of drug concentration may be reasonably interpreted as an ideal dose-response curve which might be obtained if the drug were introduced directly at the receptor. The implications of the findings with respect to receptor operation are discussed. Although the binding constants have not been found under physiological conditions, the results indicate that the receptor mechanism remains essentially intact in the brain membrane preparation.