Effects of acute administration of L-arginine on morphine antinociception and morphine distribution in central and peripheral tissues of mice.
The effect of acute treatment with L-arginine, a substrate for nitric oxide synthase (NOS) that forms NO, an important second messenger, on morphine antinociception and distribution of morphine in central and peripheral tissues of male Swiss-Webster mice was determined. The antinociception activity of morphine (10 mg/kg, s.c.) was attenuated by 400 and 800 mg/kg doses of L-arginine, but a lower dose (200 mg/kg) had no effect. D-Arginine (200-800 mg/kg) did not modify morphine antinociception. The dose of L-arginine (200 mg/kg) that did not modify morphine antinociception also did not alter the distribution of morphine in brain regions and spinal cord. A dose of 800 mg/kg of L-arginine produced a significant decrease in the concentration of morphine in midbrain and spinal cord. The highest dose of L-arginine (800 mg/kg) also increased the concentration of morphine in spleen. None of the doses of L-arginine modified the concentration of morphine in serum or urine. The results suggests that acute activation of the NO system attenuates morphine antinociception possibly by inhibiting its uptake in central sites (midbrain and spinal cord) involved in antinociceptive actions.
Department of Pharmaceutics and Pharmacodynamics (M/C 865), The University of Illinois at Chicago, Health Sciences Center, 60612, USA.
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Bhargava
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Bian
D000701:Analgesics, Opioid / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002490:Central Nervous System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D051379:Mice; D009020:Morphine / Q000493:pharmacokinetics* / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D017933:Peripheral Nervous System / Q000378:metabolism*; D013237:Stereoisomerism; D014018:Tissue Distribution
D000701:Analgesics, Opioid; D009569:Nitric Oxide; D009020:Morphine; D001120:Arginine