Abstract
An antisense oligodeoxynucleotide directed against the 5'-untranslated region of MOR-1 blocks the analgesic actions of the mu 1 analgesics morphine and [D-Ala2,D-Leu5]enkephalin (DADL) when they are microinjected into the periaqueductal gray. In contrast, morphine-6 beta-glucuronide (M6G) analgesia is unaffected by this treatment. Antisense oligodeoxynucleotides directed against distinct Gi alpha subunits also distinguish between morphine and M6G analgesia. A probe targeting Gi alpha 2 blocks morphine analgesia, as previously reported, but is inactive against M6G analgesia. Conversely, an antisense oligodeoxynucleotide against Gi alpha 1 inhibits M6G analgesia without affecting morphine analgesia. The antisense oligodeoxynucleotide directed against G(o)alpha is ineffective against both compounds. These results confirm the prior association of Gi alpha 2 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 alpha subunit antisense oligodeoxynucleotides.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Analgesics / pharmacology
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Analgesics, Opioid / antagonists & inhibitors*
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Analgesics, Opioid / pharmacology
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Animals
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Base Sequence
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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Enkephalin, Leucine-2-Alanine / antagonists & inhibitors
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Enkephalin, Leucine-2-Alanine / pharmacology
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Enkephalins / antagonists & inhibitors
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Enkephalins / pharmacology
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GTP-Binding Proteins / drug effects
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GTP-Binding Proteins / genetics*
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Male
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Microinjections
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Molecular Sequence Data
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Morphine / antagonists & inhibitors*
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Morphine / pharmacology
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Morphine Derivatives / antagonists & inhibitors*
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Morphine Derivatives / pharmacology
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Naloxone / pharmacology
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Narcotic Antagonists / pharmacology
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Oligonucleotides, Antisense / administration & dosage
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Oligonucleotides, Antisense / pharmacology*
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Periaqueductal Gray / physiology
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Rats
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Rats, Sprague-Dawley
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Receptors, Opioid, mu / drug effects
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Receptors, Opioid, mu / genetics*
Substances
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Analgesics
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Analgesics, Opioid
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Enkephalins
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Morphine Derivatives
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Narcotic Antagonists
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Oligonucleotides, Antisense
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Receptors, Opioid, mu
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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Naloxone
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Enkephalin, Leucine-2-Alanine
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morphine-6-glucuronide
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Morphine
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GTP-Binding Proteins