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Functional interaction among opioid receptor types: up-regulation of mu- and delta-opioid receptor functions after repeated stimulation of kappa-opioid receptors.
Neuropharmacology. 2004 Mar; 46(4):531-40.N

Abstract

It has been widely accepted that repeated administration of kappa-opioid receptor agonists leads to the development of antinociceptive tolerance. The present study was designed to investigate the effect of repeated administration of a selective kappa-opioid receptor agonist (1S-trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide hydrochloride ((-)U-50,488H) on the mu- and delta-opioid receptor agonist-induced antinociception and G-protein activation in mice. The mice were injected either subcutaneously (s.c.) or intracerebroventricularly (i.c.v.) pretreated with saline or (-)U-50,488H once a day for seven consecutive days. Two hours after the last injection, the mice were challenged by either mu- or delta-opioid receptor agonist for the antinociceptive assay. Repeated treatment with (-)U-50,488H (s.c. or i.c.v.) significantly enhanced antinociceptive effect of both mu-opioid receptor agonist (morphine) and delta-opioid receptor agonists ([d-Ala2]deltorphin (DELT) and (+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dime thyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC-80) compared to saline-treated groups. Under these conditions, repeated s.c. injection of (-)U-50,488H significantly enhanced both mu- and delta-opioid receptor agonist-stimulated [35S]GTPgammaS binding in the membrane of the thalamus. On the contrary, either repeated administration of morphine (s.c. or i.c.v.) or SNC-80 failed to affect the kappa-opioid receptor agonist-induced antinociception and G-protein activation. Taken together, these results suggest that repeated stimulation of kappa-opioid receptor markedly increases the functional mu- and delta-opioid receptors, whereas repeated stimulation of either mu- or delta-opioid receptor had no direct effect on kappa-opioidergic function in mice.

Authors+Show Affiliations

Department of Toxicology, Hoshi University, School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-Ku, Tokyo 142-8501, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

14975677

Citation

Khotib, Junaidi, et al. "Functional Interaction Among Opioid Receptor Types: Up-regulation of Mu- and Delta-opioid Receptor Functions After Repeated Stimulation of Kappa-opioid Receptors." Neuropharmacology, vol. 46, no. 4, 2004, pp. 531-40.
Khotib J, Narita M, Suzuki M, et al. Functional interaction among opioid receptor types: up-regulation of mu- and delta-opioid receptor functions after repeated stimulation of kappa-opioid receptors. Neuropharmacology. 2004;46(4):531-40.
Khotib, J., Narita, M., Suzuki, M., Yajima, Y., & Suzuki, T. (2004). Functional interaction among opioid receptor types: up-regulation of mu- and delta-opioid receptor functions after repeated stimulation of kappa-opioid receptors. Neuropharmacology, 46(4), 531-40.
Khotib J, et al. Functional Interaction Among Opioid Receptor Types: Up-regulation of Mu- and Delta-opioid Receptor Functions After Repeated Stimulation of Kappa-opioid Receptors. Neuropharmacology. 2004;46(4):531-40. PubMed PMID: 14975677.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional interaction among opioid receptor types: up-regulation of mu- and delta-opioid receptor functions after repeated stimulation of kappa-opioid receptors. AU - Khotib,Junaidi, AU - Narita,Minoru, AU - Suzuki,Masami, AU - Yajima,Yoshinori, AU - Suzuki,Tsutomu, PY - 2003/06/06/received PY - 2003/08/29/revised PY - 2003/10/31/accepted PY - 2004/2/21/pubmed PY - 2004/5/29/medline PY - 2004/2/21/entrez SP - 531 EP - 40 JF - Neuropharmacology JO - Neuropharmacology VL - 46 IS - 4 N2 - It has been widely accepted that repeated administration of kappa-opioid receptor agonists leads to the development of antinociceptive tolerance. The present study was designed to investigate the effect of repeated administration of a selective kappa-opioid receptor agonist (1S-trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide hydrochloride ((-)U-50,488H) on the mu- and delta-opioid receptor agonist-induced antinociception and G-protein activation in mice. The mice were injected either subcutaneously (s.c.) or intracerebroventricularly (i.c.v.) pretreated with saline or (-)U-50,488H once a day for seven consecutive days. Two hours after the last injection, the mice were challenged by either mu- or delta-opioid receptor agonist for the antinociceptive assay. Repeated treatment with (-)U-50,488H (s.c. or i.c.v.) significantly enhanced antinociceptive effect of both mu-opioid receptor agonist (morphine) and delta-opioid receptor agonists ([d-Ala2]deltorphin (DELT) and (+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dime thyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC-80) compared to saline-treated groups. Under these conditions, repeated s.c. injection of (-)U-50,488H significantly enhanced both mu- and delta-opioid receptor agonist-stimulated [35S]GTPgammaS binding in the membrane of the thalamus. On the contrary, either repeated administration of morphine (s.c. or i.c.v.) or SNC-80 failed to affect the kappa-opioid receptor agonist-induced antinociception and G-protein activation. Taken together, these results suggest that repeated stimulation of kappa-opioid receptor markedly increases the functional mu- and delta-opioid receptors, whereas repeated stimulation of either mu- or delta-opioid receptor had no direct effect on kappa-opioidergic function in mice. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/14975677/Functional_interaction_among_opioid_receptor_types:_up_regulation_of_mu__and_delta_opioid_receptor_functions_after_repeated_stimulation_of_kappa_opioid_receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028390803004234 DB - PRIME DP - Unbound Medicine ER -