Use of antisense oligodeoxynucleotide to delta-opioid receptor mRNA in the study of turnover of delta-opioid receptors in the spinal cord of the mouse.
Pretreatment of male ICR mice with an antisense oligodeoxynucleotide to delta-opioid receptor mRNA (DOR AS oligo, 163 pmol) given intrathecally (i.t.) once a day for 1-3 days produced a time-dependent attenuation of antinociception produced by i.t.-challenged [D-Ala2] deltorphin II (6.4 nmol), a delta-opioid receptor agonist. The attenuation of the [D-Ala2]deltorphin II-induced antinociception caused by pretreatment with DOR AS oligo given i.t. daily was blocked by co-pretreatment with naltriben (14.5 nmol), a delta-opioid receptor antagonist, but was markedly enhanced by concomitant pretreatment with thiorphan (19.7 nmol) or bestatin (14.5 nmol), which inhibits the degradation of endogenously released Met-enkephalin. Concomitant pretreatment with antiserum to Met-enkephalin, but not with antiserum to Leu-enkephalin, beta-endorphin or dynorphin A (1-17), and DOR AS oligo given i.t. daily for 3 days prevented the attenuation of i.t.-challenged [D-Ala2]deltorphin II-induced antinociception caused by the DOR AS oligo pretreatment. Our results support the existence of a turnover of delta-opioid receptors in the mouse spinal cord caused by the release of Met-enkephalin.
Narita
M
M
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Mizoguchi
H
H
Nagase
H
H
Tseng
L F
LF
D000818:Animals; D004744:Enkephalin, Methionine / Q000008:administration & dosage / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D011480:Protease Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis*; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D015244:Thiorphan / Q000008:administration & dosage / Q000494:pharmacology
D009292:Narcotic Antagonists; D016376:Oligonucleotides, Antisense; D009842:Oligopeptides; D011480:Protease Inhibitors; D012333:RNA, Messenger; D017465:Receptors, Opioid, delta; C068868:naltrindole benzofuran; C060209:deltorphin II, Ala(2)-; D004744:Enkephalin, Methionine; D009271:Naltrexone; D015244:Thiorphan