RT Journal Article
SR Electronic
T1 Antisense Mapping of MOR-1 in Rats: Distinguishing between Morphine and Morphine-6β-glucuronide Antinociception
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 109
OP 114
VO 281
IS 1
A1 Grace C. Rossi
A1 Liza Leventhal
A1 Ying-Xin Pan
A1 Jessica Cole
A1 Wendy Su
A1 Richard J. Bodnar
A1 Gavril W. Pasternak
YR 1997
UL http://jpet.aspetjournals.org/content/281/1/109.abstract
AB 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 M6G, 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. The American Society for Pharmacology and Experimental Therapeutics