Antisense mapping KOR-1: evidence for multiple kappa analgesic mechanisms.
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.
Pasternak
K R
KR
Department of Neurology, The George C. Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. pasterng@mskmail.mskcc.org
Rossi
G C
GC
Zuckerman
A
A
Pasternak
G W
GW
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000378:metabolism / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D016375:Antisense Elements (Genetics); D001665:Binding Sites / Q000235:genetics; D002874:Chromosome Mapping; D004399:Dynorphins / Q000378:metabolism / Q000494:pharmacology; D004723:Endorphins / Q000378:metabolism / Q000494:pharmacology; D015640:Ion Channel Gating / Q000235:genetics*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011498:Protein Precursors / Q000378:metabolism / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D018712:Analgesics, Non-Narcotic; D016375:Antisense Elements (Genetics); D004723:Endorphins; D011498:Protein Precursors; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C025681:alpha-neoendorphin; D004399:Dynorphins; C036200:rimorphin