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Altered Transition Between Agonist‐and Antagonist‐Favoring States of μ‐Opioid Receptor in Brain Membranes with Modified Microviscosity
Author(s) -
Lazar Dan F.,
Medzihradsky Fedor
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb03630.x
Subject(s) - microviscosity , chemistry , agonist , antagonist , opioid receptor , agonist antagonist , medicine , pharmacology , naltrindole , endocrinology , receptor , membrane , biophysics , biochemistry , biology
In unmodified synaptosomal brain membranes the presence of NaCl inhibited the binding to μ receptors of the tritiated opioid agonists etorphine, Tyr‐D‐Ala‐Gly‐(Me)Phe‐Gly‐ol, and sufentanil by 53, 43, and 37%, respectively, and increased that of the antagonist [ 3 H]naltrexone by 54%. On the other hand, in membranes whose microviscosity was increased by incorporation of cholesteryl hemi‐succinate (CHS) the effects of sodium on opioid agonist and antagonist binding were abolished and strongly reduced, respectively. Furthermore, in the modified membranes the ability of sodium to protect the opioid receptor from inactivation by the sulfhydryl‐reactive agent N ‐ethyl‐maleimide (NEM) was diminished. In CHS‐treated membranes whose elevated microviscosity was reduced by the incorporation of oleic acid, the effectiveness of sodium in modulating opioid binding and attenuating receptor inactivation by NEM was restored. The results implicate membrane microviscosity in the mechanism by which sodium modulates the conversion between agonist‐and antagonist‐favoring states of μ opioid receptor.