Antisense mapping of MOR-1 in rats: Distinguishing between morphine and morphine-6β-glucuronide antinociception Journal Article
| Authors: | Rossi, G. C.; Leventhal, L.; Pan, Y. X.; Cole, J.; Su, W.; Bodnar, R. J.; Pasternak, G. W. |
| Article Title: | Antisense mapping of MOR-1 in rats: Distinguishing between morphine and morphine-6β-glucuronide antinociception |
| Abstract: | In an effort to correlate the recently cloned MOR-1 receptor with the pharmacological actions of morphine and morphine-6β-glucuronide (M6G), we have used an antisense paradigm. Rats were injected intracerebroventricularly (i.c.v.) with antisense oligodeoxynucleotides on days 1, 3 and 5 and tested for analgesia on day 6 after administration of morphine or M6G i.c.v. or after microinjection of morphine directly into either the periaqueductal gray or the locus coeruleus. When given i.c.v., the antisense oligodeoxynucleotide targeting the 5'-untranslated region of exon 1 significantly decreased the analgesic actions of morphine administered i.c.v. or microinjected directly into the periaqueductal gray or locus coeruleus, with the most profound inhibition occurring in the periaqueductal gray. Thus, antisense oligodeoxynucleotides administered into the lateral ventricle can diffuse into the brainstem and interfere with morphine actions. A mismatch antisense oligodeoxynucleotide with the same base composition in which the sequence of four bases was changed was inactive. This same exon 1 antisense oligodeoxynucleotide, which was active against morphine analgesia, failed to block M6G analgesia. In contrast, antisense sequences from exons 2 and 3 decreased MSG, and not morphine, analgesia. The antisense oligodeoxynucleotide against exon 4 slightly decreased both morphine and M6G antinociception. These results confirm the antisense mapping studies on exons 1, 2 and 3 of MOR-1 in mice, which implied the presence of a novel μ receptor subtype responsible for M6G analgesia that may represent a splice variant of MOR-1. Unlike in mice, the probe against exon 4 had a small effect on M6G analgesia. |
| Keywords: | controlled study; exons; nonhuman; animals; animal experiment; animal model; locus ceruleus; rat; rats; rats, sprague-dawley; morphine; analgesics, opioid; analgesia; sodium chloride; mu opiate receptor; receptors, opioid, mu; tail flick test; morphine 6 glucuronide; oligonucleotides, antisense; deltorphin; antinociception; antisense oligodeoxynucleotide; periaqueductal gray matter; morphine derivatives; intracerebroventricular drug administration; male; priority journal; article; intracerebral drug administration |
| Journal Title: | Journal of Pharmacology and Experimental Therapeutics |
| Volume: | 281 |
| Issue: | 1 |
| ISSN: | 0022-3565 |
| Publisher: | American Society for Pharmacology and Experimental Therapeutics |
| Date Published: | 1997-04-01 |
| Start Page: | 109 |
| End Page: | 114 |
| Language: | English |
| PUBMED: | 9103486 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
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