Differential blockade of morphine and morphine-6β-glucuronide analgesia by antisense oligodeoxynucleotides directed against MOR-1 and G-protein α subunits in rats Journal Article

  

Authors:	Rossi, G. C.; Standifer, K. M.; Pasternak, G. W.
Article Title:	Differential blockade of morphine and morphine-6β-glucuronide analgesia by antisense oligodeoxynucleotides directed against MOR-1 and G-protein α subunits in rats
Abstract:	An antisense oligodeoxynucleotide directed against the 5′-untranslated region of MOR-1 blocks the analgesic actions of the μ1 analgesics morphine and [d-Ala2,d-Leu5jenkephalin (DADL) when they are microinjected into the periaqueductal gray. In contrast, morphine-6β-glucuronide (M6G) analgesia is unaffected by this treatment. Antisense oligodeoxynucleotides directed against distinct Giα subunits also distinguish between morphine and M6G analgesia. A probe targeting Giα2 blocks morphine analgesia, as previously reported, but is inactive against M6G analgesia. Conversely, an antisense oligodeoxynucleotide against GiαI inhibits M6G analgesia without affecting morphine analgesia. The antisense oligodeoxynucleotide directed against G0α is ineffective against both compounds. These results confirm the prior association of Giα2 with morphine analgesia and strongly suggests that M6G acts through a different opioid receptor, as revealed by its insensitivity towards the MOR-1 antisense probe and differential sensitivity towards G-protein α subunit antisense oligodeoxynucleotides. © 1995.
Keywords:	controlled study; unclassified drug; nonhuman; animal; animal tissue; animal experiment; gtp-binding proteins; molecular sequence data; rat; base sequence; rats; protein subunit; rats, sprague-dawley; morphine; analgesics, opioid; analgesics; guanine nucleotide binding protein; analgesia; mu opiate receptor; receptors, opioid, mu; receptor binding; tail flick test; naloxone; microinjections; oligonucleotides, antisense; enkephalin, ala(2)-mephe(4)-gly(5)-; antisense oligodeoxynucleotide; enkephalin[2 dextro alanine 4 methylphenylalanine 5 glycine]; periaqueductal gray matter; periaqueductal gray; narcotic antagonists; morphine derivatives; male; priority journal; article; enkephalin, leucine-2-alanine; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; enkephalins; enkephalin[2 dextro alanine 5 dextro leucine]; morphine-6β-glucuronide; morphine glucuronide
Journal Title:	Neuroscience Letters
Volume:	198
Issue:	2
ISSN:	0304-3940
Publisher:	Elsevier Science, Inc.
Date Published:	1995-09-29
Start Page:	99
End Page:	102
Language:	English
DOI:	10.1016/0304-3940(95)11977-5
PUBMED:	8592651
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0028856752&doi=10.1016%2f0304-3940%2895%2911977-5&partnerID=40&md5=1a3ef3c21e4cf73b4d7c52fe31b0fb65
Notes:	Article -- Export Date: 28 August 2018 -- Source: Scopus

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