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Effects of antisense oligodeoxynucleotides against opioid receptors on the receptor mRNA contents

T Oka1, M Yoshikawa, T Kobayashi

  • 1Department of Pharmacology, School of Medicine, Tokai University, Isehara, Japan. okatetsu@is.icc.u-tokai.ac.jp

Life Sciences
|May 19, 2001
PubMed

Insights

Antisense oligodeoxynucleotides (AS ODNs) targeting opioid receptors in the rat brain’s periaqueductal gray (PAG) show specific mRNA reduction and a non-specific enhancing effect on MOR mRNA reduction.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Previous studies established that antisense oligodeoxynucleotides (AS ODNs) targeting mu-opioid receptors (MOR) decrease MOR mRNA in the periaqueductal gray (PAG).
  • The enhancing effect of MOR AS ODN pretreatment on MOR mRNA reduction was previously observed.

Purpose of the Study:

  • To investigate the effect of AS ODNs against kappa-opioid receptor (KOR) and delta-opioid receptor (DOR) on MOR mRNA levels.
  • To determine if KOR or DOR AS ODN pretreatment enhances the MOR mRNA-decreasing effect of MOR AS ODN.

Main Methods:

  • Microinjection of AS ODNs targeting MOR, KOR, and DOR into the rat PAG.
  • Quantitative analysis of target and MOR mRNA content following AS ODN administration.
  • Pretreatment with KOR or DOR AS ODNs followed by MOR AS ODN administration.

Main Results:

  • KOR and DOR AS ODNs specifically reduced their respective target mRNA levels.
  • Neither KOR nor DOR AS ODNs significantly altered MOR mRNA content on their own.
  • Pretreatment with KOR or DOR AS ODNs significantly enhanced the decrease in MOR mRNA content induced by MOR AS ODN.

Conclusions:

  • AS ODNs exhibit both specific mRNA-reducing activity and a non-specific enhancing action on AS ODN-induced mRNA reduction.
  • These findings suggest complex regulatory interactions between different opioid receptor systems at the mRNA level in the PAG.

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