Differential mechanism of G-protein activation induced by endogenous mu-opioid peptides, endomorphin and beta-endorphin.
It is well documented that the mu-opioid receptor (MOP-R) is expressed by neurons in several central nervous system regions. Its occupancy with agonist drugs modulate a variety of physiological processes including pain, reward, stress, immune responses, neuroendocrine functions, and cardiovascular control. Based on the receptor binding assay, endomorphin-1 and endomorphin-2 have the highest specificity and affinity for the MOP-R of any endogenous substance so far described in the mammalian nervous system. In contrast, beta-endorphin exhibits the strongest actions among endogenous opioid peptides mainly through the MOP-R; however, it also shows the distinct pharmacological actions. Recent cloning and expression studies have indicated that MOP-Rs are seven-transmembrane domain receptors whose actions are mediated through activation of heterotrimeric guanine nucleotide binding proteins (G-proteins). The activation of G-proteins by MOP-Rs can be measured by assessing agonist-induced stimulation of membrane binding of guanosine-5'-o-(3-[35S]thio)triphosphate ([35S]GTPgammaS). The subject of the present review is to focus on the differential mechanism underlying G-protein activation induced by these mu-opioid peptides using the [35S]GTPgammaS binding assay.
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA. toyama@mcw.edu
Hirokazu
H
Mizoguchi
Leon F
LF
Tseng
Tsutomu
T
Suzuki
Ichiro
I
Sora
Minoru
M
Narita
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology; D018847:Opioid Peptides / Q000378:metabolism / Q000494:pharmacology; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism*; D001615:beta-Endorphin / Q000378:metabolism* / Q000494:pharmacology
D009842:Oligopeptides; D018847:Opioid Peptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; C105294:endomorphin 2; D001615:beta-Endorphin; D019204:GTP-Binding Proteins