RT Journal Article
SR Electronic
T1 Spinal Pretreatment with Antisense Oligodeoxynucleotides against Exon-1, -4, or -8 of μ-Opioid Receptor Clone Leads to Differential Loss of Spinal Endomorphin-1-and Endomorphin-2-Induced Antinociception in the Mouse
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 867
OP 873
DO 10.1124/jpet.102.038810
VO 303
IS 2
A1 Hsiang-en Wu
A1 Hirokazu Mizoguchi
A1 Maia Terashvili
A1 Randy J. Leitermann
A1 Kuei-chun Hung
A1 James M. Fujimoto
A1 Leon F. Tseng
YR 2002
UL http://jpet.aspetjournals.org/content/303/2/867.abstract
AB Intrathecal (i.t.) pretreatments with antisense oligodeoxynucleotides (AS ODNs) against exon-1, -4, or -8 of μ-opioid receptor clone (MOR-1) to knockdown different variants of MOR-1 on the antinociception induced by endomorphin-1, enomorphin-2, or [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) given i.t. were investigated in male CD-1 mice. The antinociception was measured with the tail-flick test. AS ODNs against exon-1 (5 μg) given i.t. once daily for 3 days attenuated the antinociception induced by endomorphin-1 and endomorphin-2 with the dose-response curves shifted to the right by 4.5- and 5.3-fold, respectively. AS ODNs against exon-4 (5 μg) attenuated the antinociception induced by endomorphin-1 and endomorphin-2 with the dose-response curves shifted to the right by 2.4- and 5.3-fold, respectively. However, AS ODNs against exon-8 (5 μg) attenuated only the antinociception induced by endomorphin-1, but not endomorphin-2 with the dose-response curves shifted to the right by 3.9- and 1.3-fold, respectively. One more day of pretreatment with antisense probes failed to further reduce the antinociception. The antinociception induced by DAMGO was attenuated by i.t. pretreatment with AS ODNs directed against exon-1, and, to a lesser extent, by AS ODNs directed against exon-8. The mismatch AS ODNs against respective exon-1, -4, and -8 failed to exert significant effects. The selective actions of antisense probes directed against different exons of the MOR-1 in attenuating the antinociception induced by endomorphin-1, endomorphin-2, and DAMGO suggest that multiple splice variants of the MOR-1 exist and support the view that different subtypes of μ-opioid receptors are involved in antinociception induced by endomorphin-1, endomorphin-2, and DAMGO. The American Society for Pharmacology and Experimental Therapeutics