Enhancement of the rate of GTP hydrolysis in rat brain by repeated kappa-opioid treatment.
To investigate the G protein and protein kinase C (PKC) systems during the initial state of kappa-opioid tolerance, the low Km GTPase and PKC activities were measured following repeated treatment of rat with the kappa-agonist, U-50,488. In behavioral studies, antinociceptive tolerance to U-50,488 was developed following 7-day treatment with U-50,488. Under these conditions, repeated administration of U-50,488 significantly enhanced the basal low Km GTPase activity in the pons/medulla but not in the cortex and midbrain regions. On the other hand, repeated U-50,488 treatment had no effect on PKC activity in cytosol and membrane fractions under the calcium-chelating conditions. These results indicate that repeated administration of kappa-agonist, U-50,488, increases in the basal hydrolysis of GTP to GDP in rat pons/medulla but not PKC activity which was observed in the case of repeated administration with morphine in rats.
Feng
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Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Narita
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Makimura
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Hoskins
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Ho
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D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004361:Drug Tolerance / Q000502:physiology; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006868:Hydrolysis / Q000187:drug effects; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D011759:Pyrrolidines; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D006160:Guanosine Triphosphate; D011493:Protein Kinase C; D020558:GTP Phosphohydrolases