Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neurochemical and functional correlates of opioid receptor up-regulation after chronic antagonist administration in vivo and of down-regulation after withdrawal of antagonist were examined. Total brain opioid receptors increased 1.9-fold by day 8 of naltrexone administration, after which no further increase was observed; the newly synthesized or unmasked receptors exhibited an enhanced sensitivity to guanyl nucleotide modulation. Withdrawal from chronic naltrexone treatment resulted in a return to nearly control levels of receptor density and guanyl nucleotide sensitivity in a period of 6 days. These results suggest that up-regulation is accompanied by an increased coupling of the receptors to the inhibitory guanyl nucleotide binding protein (Ni) and that down-regulation involves the dissociation of the receptor/Ni complex. In experiments designed to target opiate receptor subtypes, long-term treatment with naltrexone was found to produce a coordinated up-regulation of brain mu and delta receptors, but did not cause a significant change in the density or affinity of kappa or sigma receptors. These findings indicate that the kappa and sigma opiate receptor classes may be subject to independent control mechanisms. Chronic naltrexone treatment also resulted in an enhanced morphine-induced analgesia. This result indicates that a functional supersensitivity occurs as a result of the selective up-regulation of mu and delta receptors. After withdrawal from naltrexone, supersensitivity to morphine-induced analgesia decreased monotonically and, in parallel to opioid receptor density, to prenaltrexone treatment levels within 6 days. Together, these results suggest a functional significance for antagonist-induced mu and delta opiate receptor up-regulation.
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PMID:Neurochemical and functional correlates of naltrexone-induced opiate receptor up-regulation. 298 11

The developmental changes in mu opiate receptor-mediated antinociception and coupling to guanyl nucleotide binding proteins were studied in the rat. ED50 values for morphine- and sufentanil-induced antinociception were determined in the paw-lift assay on days 10 and 27. The ED50 for morphine analgesia in 10-day-old pups was 0.35 mg/kg and increased with age to 5.3 mg/kg on day 27. Similarly, sufentanil was more potent in pups than in weanlings, the ED50 increasing from 1.7 to 7.6 micrograms/kg. Serum and brain morphine levels after 5 mg/kg of morphine were higher in neonates (day 10) than weanlings (day 27), largely due to a more rapid redistribution phase in weanlings (T1/2 = 26 min.) than in pups (T1/2 = 2.5 hr). Additionally, a substantial (70%) antinociceptive response was achieved in neonates at brain morphine levels that were one-half those producing an equal effect in weanlings. Radioligand binding studies indicated that the number of mu receptors increased 2-fold without change in affinity between days 10 and 27, whereas the GTP analog guanylylimidophosphate was nearly twice as effective in shifting the mu receptors from high to low affinity on day 27 than on day 10. These data indicate that neonatal rats are more sensitive to mu opiate antinociception despite apparently weaker receptor-guanyl nucleotide binding protein coupling. This greater sensitivity is enhanced by the pharmacokinetic differences between neonates and weanlings which result in higher drug levels in pups after a similar dose.
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PMID:Increased sensitivity to mu opiate antinociception in the neonatal rat despite weaker receptor-guanyl nucleotide binding protein coupling. 779 Nov 8