kappa-Opioid receptor agonist protects against ischemic reduction of 2-deoxyglucose uptake in morphine-tolerant rats.
We examined the effects of mu-opioid receptor agonist and antagonists, and kappa-opioid receptor agonist on the hypoxia/hypoglycemia-induced reduction in 2-deoxyglucose uptake of rat hippocampal slices. Naloxone, a mu-opioid receptor antagonist and (5,7,8)-(+)-3,4-dichloro-N-methyl-N-(7,8,1-pyrrolidinyl)-1-oxaspirol+ ++ (4,5)dec-8-yl)-benzeneacetamide methanesulfonate, U-62,066E, a kappa-opioid receptor receptor agonist, showed neuroprotective actions against the hypoxia/hypoglycemia-induced deficit in glucose uptake. In contrast, morphine exhibited an exacerbating action. These results suggest that blockade of mu-opioid receptor- and stimulation of kappa-opioid receptor-mediated functions has a protective role against the hypoxia/hypoglycemia-induced decreases in glucose metabolism in hippocampal slices. Chronic administration of morphine (10 mg/kg) for 9 days affected neither the basal nor the hypoxia/hypoglycemia-induced reduction in 2-deoxyglucose uptake. Rats treated with morphine chronically exhibited not only tolerance to the analgesic effect but also tolerance to the exacerbating action. However, chronic morphine did not modify U-62,066E-induced neuroprotection. These findings indicate that the receptor mechanisms of neuroprotection produced by the activation of kappa-opioid receptors may not be involved in mu-opioid receptor function.
Shibata
S
S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Tominaga
K
K
Watanabe
S
S
D000700:Analgesics / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology; D002545:Brain Ischemia / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism*; D004361:Drug Tolerance; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007003:Hypoglycemia / Q000378:metabolism; D002534:Hypoxia, Brain / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000037:antagonists & inhibitors
D000700:Analgesics; D000701:Analgesics, Opioid; D001575:Benzomorphans; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D009270:Naloxone; C027247:MR 2266; D009020:Morphine; D003847:Deoxyglucose; C051272:spiradoline