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Endomorphin‐Stimulated [ 35 S]GTPγS Binding in Rat Brain: Evidence for Partial Agonist Activity at μ‐Opioid Receptors
Author(s) -
Sim Laura J.,
Liu Qixu,
Childers Steven R.,
Selley Dana E.
Publication year - 1998
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 - 10.1046/j.1471-4159.1998.70041567.x
Subject(s) - damgo , chemistry , agonist , receptor , gtp' , g protein , medicine , lateral parabrachial nucleus , endocrinology , opioid receptor , parabrachial nucleus , biochemistry , biology , hypothalamus , enzyme
Endomorphin‐1 is a peptide whose binding selectivity suggests a role as an endogenous ligand at μ‐opioid receptors. In the present study, the effect of endomorphin‐1 on μ receptor‐coupled G proteins was compared with that of the μ agonist DAMGO by using agonist‐stimulated [ 35 S]GTPγS binding in rat brain. [ 35 S]GTPγS autoradiography revealed a similar localization of endomorphin‐1 and DAMGO‐stimulated [ 35 S]GTPγS binding in areas including thalamus, caudate‐putamen, amygdala, periaqueductal gray, parabrachial nucleus, and nucleus tractus solitarius. Naloxone blocked endomorphin‐1‐stimulated labeling in all regions examined. Although the distribution of endomorphin‐1‐stimulated [ 35 S]GTPγS binding resembled that of DAMGO, the magnitude of endomorphin‐1‐stimulated binding was significantly lower than that produced by DAMGO. Concentration‐effect curves of endomorphin‐1 and DAMGO in thalamic membranes confirmed that endomorphin‐1 produced only 70% of DAMGO‐stimulated [ 35 S]GTPγS binding. Differences in maximal stimulation of [ 35 S]GTPγS binding between DAMGO and endomorphin‐1 were magnified by increasing GDP concentrations, and saturation analysis of net endomorphin‐1‐stimulated [ 35 S]GTPγS binding revealed a lower apparent B max value than that obtained with DAMGO. Endomorphin‐1 also partially antagonized DAMGO stimulation of [ 35 S]GTPγS binding. These results demonstrate that endomorphin‐1 is a partial agonist for G protein activation at the μ‐opioid receptor in brain.