Decreased opioid-induced antinociception but unaltered G-protein activation in the genetic-diabetic NOD mouse.
Previous evaluation of antinociceptive action in experimental diabetes has been conducted almost exclusively in chemically induced diabetes mellitus. The purpose of the present study was to evaluate antinociceptive response and G-protein activation by mu-opioid receptor and delta-opioid receptor agonists in the genetic non-obese diabetic (NOD) mouse, a model of type I insulin-dependent diabetes mellitus (IDDM). Tail-flick latency before and after hyperglycemia was unaltered. Hyperglycemic NOD mice were hyporesponsive to intracerebroventricular (i.c.v.) injections of [D-Ala(2)]deltorphin II but not to [D-Ala(2), N-MePhe(4), Gly-ol(5)]enkephalin (DAMGO); however, G-protein activation in pons/medulla assessed by [35S]GTPgammaS binding was not diminished. This suggests that a G-protein defect in signaling cannot account for the hyporesponsiveness of antinociception in this genetic model of IDDM.
Department of Surgery, Division of Transplant Surgery, Medical College of Wisconsin, Froedtert Memorial Lutheran Hospital, 9200 West Wisconsin Avenue, 53226, Milwaukee, WI, USA. gmpieper@mcw.edu
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Pieper
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Mizoguchi
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Ohsawa
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Kamei
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Nagase
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Tseng
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000503:physiopathology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology*; D005260:Female; D019204:GTP-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D007276:Injections, Intraventricular; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D009619:Nociceptors / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology; D010146:Pain / Q000517:prevention & control*; D010879:Piperazines / Q000494:pharmacology; D011149:Pons / Q000187:drug effects / Q000378:metabolism; D011957:Receptors, Opioid / Q000819:agonists / Q000378:metabolism; D013462:Sulfur Radioisotopes
D000701:Analgesics, Opioid; D001549:Benzamides; D009842:Oligopeptides; D010879:Piperazines; D011957:Receptors, Opioid; D013462:Sulfur Radioisotopes; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C060209:deltorphin II, Ala(2)-; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019204:GTP-Binding Proteins