Antisense oligodeoxynucleotide to a delta-opioid receptor selectively blocks the spinal antinociception induced by delta-, but not mu- or kappa-opioid receptor agonists in the mouse.
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.
Tseng
L F
LF
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226.
Collins
K A
KA
Kampine
J P
JP
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D011759:Pyrrolidines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism
D000700:Analgesics; D004745:Enkephalins; D016376:Oligonucleotides, Antisense; D011759:Pyrrolidines; D012333:RNA, Messenger; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D020881:Enkephalin, D-Penicillamine (2,5)-