Antisense mapping the MOR-1 opioid receptor: Evidence for alternative splicing and a novel morphine-6β-glucuronide receptor Journal Article
| Authors: | Rossi, G. C.; Pan, Y. X.; Brown, G. P.; Pasternak, G. W. |
| Article Title: | Antisense mapping the MOR-1 opioid receptor: Evidence for alternative splicing and a novel morphine-6β-glucuronide receptor |
| Abstract: | 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 mu1 action, while five of six oligodeoxynucleotides directed against exons 2 and 3 are inactive. Inhibition of gastrointestinal transit and spinal morphine analgesia, two mu2 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 mu1 and mu2 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. © 1995. |
| Keywords: | controlled study; exon; exons; drug efficacy; nonhuman; mouse; animal; mice; animal experiment; dna, antisense; cloning, molecular; gene mapping; molecular sequence data; alternative splicing; alternative rna splicing; base sequence; morphine; analgesia; mu opiate receptor; receptors, opioid, mu; morphine 6 glucuronide; gastrointestinal transit; opioid receptor; receptor subtype; antisense; antisense oligonucleotide; nucleic acid heteroduplexes; spinal anesthesia; dna probes; mu receptor; morphine derivatives; intracerebroventricular drug administration; male; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; morphine-6β-glucuronide; intrathecal drug administration; mu1 receptor; mu2 receptor |
| Journal Title: | FEBS Letters |
| Volume: | 369 |
| Issue: | 2-3 |
| ISSN: | 0014-5793 |
| Publisher: | Wiley Blackwell |
| Date Published: | 1995-08-07 |
| Start Page: | 192 |
| End Page: | 196 |
| Language: | English |
| DOI: | 10.1016/0014-5793(95)00757-z |
| PUBMED: | 7649256 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 28 August 2018 -- Source: Scopus |
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