Differential blockade of morphine and morphine-6 beta-glucuronide analgesia by antisense oligodeoxynucleotides directed against MOR-1 and G-protein alpha subunits in rats

Neurosci Lett. 1995 Sep 29;198(2):99-102. doi: 10.1016/0304-3940(95)11977-5.

Abstract

An antisense oligodeoxynucleotide directed against the 5'-untranslated region of MOR-1 blocks the analgesic actions of the mu 1 analgesics morphine and [D-Ala2,D-Leu5]enkephalin (DADL) when they are microinjected into the periaqueductal gray. In contrast, morphine-6 beta-glucuronide (M6G) analgesia is unaffected by this treatment. Antisense oligodeoxynucleotides directed against distinct Gi alpha subunits also distinguish between morphine and M6G analgesia. A probe targeting Gi alpha 2 blocks morphine analgesia, as previously reported, but is inactive against M6G analgesia. Conversely, an antisense oligodeoxynucleotide against Gi alpha 1 inhibits M6G analgesia without affecting morphine analgesia. The antisense oligodeoxynucleotide directed against G(o)alpha is ineffective against both compounds. These results confirm the prior association of Gi alpha 2 with morphine analgesia and strongly suggests that M6G acts through a different opioid receptor, as revealed by its insensitivity towards the MOR-1 antisense probe and differential sensitivity towards G-protein alpha subunit antisense oligodeoxynucleotides.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesics / pharmacology
  • Analgesics, Opioid / antagonists & inhibitors*
  • Analgesics, Opioid / pharmacology
  • Animals
  • Base Sequence
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalin, Leucine-2-Alanine / antagonists & inhibitors
  • Enkephalin, Leucine-2-Alanine / pharmacology
  • Enkephalins / antagonists & inhibitors
  • Enkephalins / pharmacology
  • GTP-Binding Proteins / drug effects
  • GTP-Binding Proteins / genetics*
  • Male
  • Microinjections
  • Molecular Sequence Data
  • Morphine / antagonists & inhibitors*
  • Morphine / pharmacology
  • Morphine Derivatives / antagonists & inhibitors*
  • Morphine Derivatives / pharmacology
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Oligonucleotides, Antisense / administration & dosage
  • Oligonucleotides, Antisense / pharmacology*
  • Periaqueductal Gray / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, mu / drug effects
  • Receptors, Opioid, mu / genetics*

Substances

  • Analgesics
  • Analgesics, Opioid
  • Enkephalins
  • Morphine Derivatives
  • Narcotic Antagonists
  • Oligonucleotides, Antisense
  • Receptors, Opioid, mu
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Naloxone
  • Enkephalin, Leucine-2-Alanine
  • morphine-6-glucuronide
  • Morphine
  • GTP-Binding Proteins