Loss of mu-opioid receptor-mediated G-protein activation in the pons/medulla of mice lacking the exons 2 and 3 of mu-opioid receptor gene.
The G-protein activation induced by mu-opioid receptor agonists in the pons/medulla membrane obtained from mice lacking exons 2 and 3 of mu-opioid receptor gene (MOR (Exons 2 and 3)-knockout (KO) mice) was investigated by monitoring guanosine-5'-o-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding. The MOR agonists D-Ala2,MePhe4,Gly(ol)5)enkephalin, endomorphin-1 and endomorphin-2 each produced concentration-dependent increases in [(35)S]GTPgammaS binding to pons/medulla membrane in wild-type mice, but not in MOR (Exons 2 and 3)-KO mice. beta-Endorphin also produced a concentration-dependent increase of [(35)S]GTPgammaS binding to pons/medulla membrane in wild-type mice, however the increase of [(35)S]GTPgammaS binding induced by beta-endorphin was partially attenuated in MOR (Exons 2 and 3)-KO mice. The present results suggest that MOR that is created from the sequences encoded with exons 2 and 3 of the MOR gene, as has been previously observed in studies of mice lacking exon 1 of this gene, may be another critical target for the activation of G-protein by MOR agonists in the mouse pons/medulla.
Mizoguchi
Hirokazu
H
Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Wu
Hsiang En
HE
Narita
Minoru
M
Loh
Horace H
HH
Nagase
Hiroshi
H
Tseng
Leon F
LF
D000701:Analgesics, Opioid / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D005091:Exons / Q000235:genetics; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D017353:Gene Deletion; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism*; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009842:Oligopeptides / Q000494:pharmacology; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D013460:Sulfur Isotopes
D000701:Analgesics, Opioid; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; D013460:Sulfur Isotopes; C105293:endomorphin 1; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C105294:endomorphin 2; D019204:GTP-Binding Proteins