Antisense mapping KOR-1: evidence for multiple kappa analgesic mechanisms

Brain Res. 1999 May 1;826(2):289-92. doi: 10.1016/s0006-8993(99)01294-9.

Abstract

In binding assays, both dynorphin B and alpha-neoendorphin are relatively selective for the kappa1b site, unlike U50,488H which has high affinity for both kappa1a and kappa1b sites. In vivo, U50,488H, dynorphin B and alpha-neoendorphin analgesia are reversed by the kappa1-selective antagonist, nor-binaltorphimine (norBNI). Antisense mapping the three exons of KOR-1 revealed that probes targeting all three exons blocked U50,488H analgesia, as expected. However, the selectivity profile of dynorphin B and alpha-neoendorphin analgesia towards the various antisense oligodeoxynucleotides differed markedly from U50,488H, implying a different receptor mechanism of action.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / metabolism
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / pharmacology
  • Analgesics, Non-Narcotic / metabolism
  • Analgesics, Non-Narcotic / pharmacology
  • Animals
  • Antisense Elements (Genetics)*
  • Binding Sites / genetics
  • Chromosome Mapping*
  • Dynorphins / metabolism
  • Dynorphins / pharmacology
  • Endorphins / metabolism
  • Endorphins / pharmacology
  • Ion Channel Gating / genetics*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Protein Precursors / metabolism
  • Protein Precursors / pharmacology
  • Receptors, Opioid, kappa / chemistry
  • Receptors, Opioid, kappa / genetics*
  • Receptors, Opioid, kappa / metabolism

Substances

  • Analgesics, Non-Narcotic
  • Antisense Elements (Genetics)
  • Endorphins
  • Protein Precursors
  • Receptors, Opioid, kappa
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • alpha-neoendorphin
  • Dynorphins
  • rimorphin