Antisense oligodeoxynucleotide to a delta-opioid receptor messenger RNA selectively blocks the antinociception induced by intracerebroventricularly administered delta-, but not mu-, epsilon- or kappa-opioid receptor agonists in the mouse.
An antisense oligodeoxynucleotide to delta-opioid receptor messenger RNA was utilized to block the expression of mouse delta-opioid receptors for antinociception. The antinociception was measured by the tail-flick test in male ICR mice. Pretreatment with delta-antisense oligodeoxynucleotide (163 pmol) given intracerebroventricularly twice a day for one to four days produced a time-dependent inhibition of the tail-flick response induced by intracerebroventricularly administered (D-Ala2)deltorphin II (12.8 nmol). The (D-Ala2)deltorphin II-induced antinociception was significantly attenuated after three to four days of the delta-antisense oligodeoxynucleotide treatment, remained attenuated for two days and gradually recovered to the control level in four to 10 days after cessation of the pretreatment with delta-antisense oligodeoxynucleotide. Pretreatment with delta-antisense oligodeoxynucleotide (163 pmol) twice a day for four days markedly attenuated the antinociception induced by intracerebroventricularly administered (D-Ala2)deltorphin II and, to a lesser extent, by D-Pen2-D-Pen5-enkephalin and morphine, but not by (D-Ala2-MePhe4-Gly(ol)5)enkephalin, beta-endorphin or U50,488H. Mismatched oligodeoxynucleotide (163 pmol) was ineffective against the antinociception induced by these opioids. Our results provide the evidence that the cloned delta-opioid receptor is related to the pharmacologically classified delta 2-opioid receptor, and the antinociception induced by (D-Ala2)deltorphin II and, at least in part, by D-Pen2-D-Pen5-enkephalin and morphine given intracerebroventricularly is mediated by the stimulation of delta 2-opioid receptors. However, delta 2-opioid receptors are not involved in the antinociception induced by beta-endorphin, (D-Ala2-MePhe4-Gly(ol)5)enkephalin or U50,488H given intracerebroventricularly.
Wang
H Q
HQ
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Kampine
J P
JP
Tseng
L F
LF
D000818:Animals; D007276:Injections, Intraventricular; D007700:Kinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D011957:Receptors, Opioid / Q000819:agonists*; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000096:biosynthesis* / Q000235:genetics; D017473:Receptors, Opioid, kappa / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists; D017480:Receptors, sigma / Q000819:agonists
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D017480:Receptors, sigma