Comparison of G-protein activation in the brain by μ-, δ-, and κ-opioid receptor agonists in μ-opioid receptor knockout mice

• Published in: Brain research bulletin 2000-07, Vol.52 (4), p.297-302
• Main Authors: Park, Younjoo, Ma, Tangeng, Tanaka, Sachiko, Jang, Choon-Gon, Loh, Horace H, Ko, Kwang Ho, Ho, Ing Kang
• Format: Article
• Language: English
• Subjects: Alleles; Analgesics, Opioid - pharmacology; Animals; Autoradiography; Benzeneacetamides; Binding, Competitive - drug effects; Biological and medical sciences; Blotting, Southern; Brain - drug effects; Brain - metabolism; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Enkephalin, Ala-MePhe-Gly- - pharmacology; Enkephalin, D-Penicillamine (2,5)- - pharmacology; Fundamental and applied biological sciences. Psychology; G-Protein coupling; GTP-Binding Proteins - metabolism; Guanosine 5'-O-(3-Thiotriphosphate) - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Pyrrolidines - pharmacology; Receptors, Opioid, delta - agonists; Receptors, Opioid, kappa - agonists; Receptors, Opioid, mu - agonists; Receptors, Opioid, mu - deficiency; Receptors, Opioid, mu - genetics; Sulfur Radioisotopes; Vertebrates: nervous system and sense organs; κ-Opioid receptor; μ-Opioid receptor knockout mice
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/S0361-9230(00)00265-3

Mice lacking the μ-opioid receptor gene have been developed by a gene knockout procedure. In this study, the activity of opioid receptor coupled G-proteins was examined to investigate whether there is a change in the extent of coupling for μ-, δ-, and κ-opioid receptors in μ-opioid receptor knockout mice. Selective agonists of μ- (DAMGO), δ- (DPDPE), and κ- (U-69,593) opioid receptors stimulated [ 35S]GTPγS binding in the caudate putamen and cortex of wild-type mice. In contrast, only U-69,593 stimulated [ 35S]GTPγS binding in these regions of μ-opioid receptor knockout mice. These results confirmed the absence of G-protein activation by a μ-opioid receptor agonist in μ-opioid receptor knockout mice, and demonstrated that coupling of the κ-opioid receptor to G-proteins is preserved in these mice. However, G-protein activation by the δ-opioid receptor agonist, DPDPE, was reduced in the μ-opioid receptor knockout mice, at least in the brain regions studied using autoradiography.