Abstract
An antisense oligodeoxynucleotide (A-oligo) to delta-opioid receptor mRNA was utilized to block the expression of mouse delta-opioid receptor in the spinal cord of male ICR mice. Intrathecal treatment with A-oligo (1.6-163 pmol) dose-dependently attenuated the antinociception induced by i.t. administered DPDPE ([D-Pen2,5]enkephalin) or [D-Ala2]deltorphin II, delta-opioid receptor agonist, without affecting the antinociception induced by DAMGO ([D-Ala2-MePhe4,Gly(ol)5]enkephalin) or U50,488H, respective mu- or kappa-opioid receptor agonists. Scrambled sense oligodeoxynucleotide (163 pmol) was ineffective against the tail-flick inhibition induced by DPDPE,[D-Ala2]deltorphin, DAMGO or U50,488H. The studies confirm previous pharmacological studies at the molecular level indicating a distinct delta-opioid receptor for antinociception in the spinal cord.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
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Analgesics / antagonists & inhibitors*
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Analgesics / 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, D-Penicillamine (2,5)-
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Enkephalins / antagonists & inhibitors
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Enkephalins / pharmacology
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Male
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Mice
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Molecular Sequence Data
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Oligonucleotides, Antisense / genetics
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Oligonucleotides, Antisense / pharmacology*
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Pyrrolidines / antagonists & inhibitors
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Pyrrolidines / pharmacology
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RNA, Messenger / metabolism
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Receptors, Opioid, delta / antagonists & inhibitors*
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Receptors, Opioid, delta / genetics
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Receptors, Opioid, delta / metabolism
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Receptors, Opioid, kappa / antagonists & inhibitors
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Receptors, Opioid, kappa / metabolism
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Receptors, Opioid, mu / antagonists & inhibitors
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Receptors, Opioid, mu / metabolism
Substances
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Analgesics
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Enkephalins
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Oligonucleotides, Antisense
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Pyrrolidines
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RNA, Messenger
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Receptors, Opioid, delta
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Receptors, Opioid, kappa
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Receptors, Opioid, mu
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
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Enkephalin, D-Penicillamine (2,5)-