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Antisense mapping the MOR‐1 opioid receptor: evidence for alternative splicing and a novel morphine‐6β‐glucuronide receptor
Author(s) -
Rossi Grace C.,
Pan Ying-Xin,
Brown George P.,
Pasternak Gavril W.
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00757-z
Subject(s) - opioid receptor , alternative splicing , receptor , morphine , chemistry , pharmacology , opioid , computational biology , microbiology and biotechnology , biology , biochemistry , gene , gene isoform
Although MOR‐1 encodes a mu opioid receptor, its relationship to the pharmacologically defined mu receptor subtypes has been unclear. Antisense mapping now suggests that these subtypes results from alternative splicing of MOR‐1. Three oligodeoxynucleotide probes targeting exon 1 and another oligodeoxynucleotide directed against the coding region of exon 4 block supraspinal morphine analgesia, a mu 1 action, while five of six oligodeoxynucleotides directed against exons 2 and 3 are inactive. Inhibition of gastrointestinal transit and spinal morphine analgesia, two mu 2 actions, are blocked only by the probe against exon 4 and not by those directed against exon 1. In contrast, the analgesic actions of the extraordinarily potent mu drug morphine‐6β‐glucuronide are blocked by six different antisense oligodeoxynucleotides targeting exons 2 and 3, but not by those acting on exons 1 or 4. These results suggest that the mu 1 and mu 2 receptor subtypes originally defined in binding and pharmacological studies result from alternative splicing of MOR‐1 while morphine‐6β‐glucuronide acts through a novel, previously unidentified receptor which is yet another MOR‐1 splice variant.