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

In binding assays, both dynorphin B and alpha-neoendorphin are relatively selective 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 alpha-neoendorphin analgesia are reversed by the kappa(1)-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. (C) 1999 Elsevier Science B.V. All rights reserved.