ALTERED TRANSITION BETWEEN AGONIST-FAVORING AND ANTAGONIST-FAVORING STATES OF MU-OPIOID RECEPTOR IN BRAIN MEMBRANES WITH MODIFIED MICROVISCOSITY

In unmodified synaptosomal brain membranes the presence of NaCl inhibi ted the binding to mu receptors of the tritiated opioid agonists etorp hine, Tyr-D-Ala-Gly-(Me)Phe-Gly-ol, and sufentanil by 53,43, and 37%, respectively, and increased that of the antagonist [H-3]naltrexone by 54%. On the other hand, in membranes whose microviscosity was increase d by incorporation of cholesteryl hemisuccinate (CHS) the effects of s odium on opioid agonist and antagonist binding were abolished and stro ngly reduced, respectively. Furthermore, in the modified membranes the ability of sodium to protect the opioid receptor from inactivation by the sulfhydryl-reactive agent N-ethylmaleimide (NEM) was diminished. In CHS-treated membranes whose elevated microviscosity was reduced by the incorporation of oleic acid, the effectiveness of sodium in modula ting opioid binding and attenuating receptor inactivation by NEM was r estored. The results implicate membrane microviscosity in the mechanis m by which sodium modulates the conversion between agonist- and antago nist-favoring states of mu opioid receptor.