endomorphin-1 and morphine-6-glucuronide

The G-protein activation induced by mu-opioid receptor agonists was determined in spinal cord membranes from two types of mu-opioid receptor knockout mice: mice with a disruption of exon 1 (MOR (Exon 1)-KO) or exons 2 and 3 (MOR (Exons 2 and 3)-KO) of the mu-opioid receptor gene. The G-protein activation induced by the opioid agonists was measured by monitoring the increases of guanosine-5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTP gamma S) binding. The mu-opioid receptor agonists (D-Ala(2),N-MePhe (4),Gly-ol(5)]enkephalin, endomorphin-1, endomorphin-2, morphine, morphine-6 beta-glucuronide, and fentanyl produced concentration-dependent increases of [(35)S]GTP gamma S binding to spinal cord membranes in wild-type mice, but not in MOR (Exon 1)-KO mice or MOR (Exons 2 and 3)-KO mice. On the other hand, the delta-opioid receptor agonist [D-Pen (2,5)]enkephalin, the kappa-opioid receptor agonist (-)U50,488H, or the ORL1-receptor agonist nociception increased [(35)S]GTP gamma S binding in the spinal cord membranes from both MOR (Exon 1)-KO mice and MOR (Exons 2 and 3)-KO mice to the same extent as in the corresponding wild-type mice. The results provide further information about the important roles of the sequences encoded within exon 1 and exons 2 and 3 of mu-opioid receptor gene for the activation of G-proteins by mu-opioid receptor agonists in the mouse spinal cord.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, D-Penicillamine (2,5)-; Exons; Fentanyl; GTP-Binding Proteins; Guanosine 5'-O-(3-Thiotriphosphate); In Vitro Techniques; Mice; Mice, Knockout; Morphine Derivatives; Nociceptin; Nociceptin Receptor; Oligopeptides; Opioid Peptides; Radioligand Assay; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Spinal Cord