In binding assays, both dynorphin B and alpha-neoendorphin are relatively s
elective for the kappa,, site, unlike U50,488H which has high affinity for
both kappa(1a) and kappa(1b) sites. In vivo, U50,488H, dynorphin B and alph
a-neoendorphin analgesia are reversed by the kappa(1)-selective antagonist,
nor-binaltorphimine (norBNI). Antisense mapping the three exons of KOR-1 r
evealed that probes targeting all three exons blocked U50,488H analgesia, a
s expected. However, the selectivity profile of dynorphin B and alpha-neoen
dorphin analgesia towards the various antisense oligodeoxynucleotides diffe
red markedly from U50,488H, implying a different receptor mechanism of acti
on. (C) 1999 Elsevier Science B.V. All rights reserved.