Use of selective antagonists and antisense oligonucleotides to evaluate the mechanisms of BUBU antinociception

Daniel M. Hutcheson, Pilar Sánchez-Blazquez, Marta Rodriguez-Diaz, Javier Garzon, Helmut Schmidhammer, Anna Borsodi, Bernard P. Roques, Rafael Maldonado

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6 Citations (Scopus)

Abstract

Evidence suggests that the antinociceptive effects of selective δ-opioid receptor agonists may involve an activation of the μ-receptor in some experimental conditions. The aim of this study was to clarify the receptors involved in the antinociceptive responses of the selective and systemically active δ-opioid receptor agonist Tyr-D-Ser-(O-tert-butyl)-Gly-Phe-Leu-Thr-(O-tert-butyl) (BUBU). The antinociception induced by systemic (i.v.) or central (i.c.v.) administration of BUBU was measured in the hot plate (jumping and paw lick latencies) and tail immersion tests in mice. In both tests, the responses were more intense when BUBU was administered by central route. The pre-treatment with the μ-opioid receptor antagonist cyprodime blocked the effects induced by central BUBU in the hot plate and tail immersion tests. The δ-opioid receptor antagonist naltrindole had no effect on BUBU-induced antinociception in the hot plate but decreased BUBU responses in the tail immersion test. Further evidence for this dual receptor action of BUBU was demonstrated by using antisense oligodeoxynucleotides. Thus, a reduction in central BUBU-induced antinociception was observed in the tail immersion test after the administration of antisense probes that selectively blocked the expression of μ- or δ-opioid receptors. These findings clearly indicate using a dual pharmacological and molecular approach that BUBU mediates its antinociceptive effects via activation of both μ- and δ-opioid receptors. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)29-37
Number of pages9
JournalEuropean Journal of Pharmacology
Volume383
Issue number1
DOIs
Publication statusPublished - Oct 21 1999

Keywords

  • Antinociception
  • Antisense oligonucleotide
  • BUBU
  • Cyprodime
  • Naltrindole
  • δ-Opioid receptor

ASJC Scopus subject areas

  • Pharmacology

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    Hutcheson, D. M., Sánchez-Blazquez, P., Rodriguez-Diaz, M., Garzon, J., Schmidhammer, H., Borsodi, A., Roques, B. P., & Maldonado, R. (1999). Use of selective antagonists and antisense oligonucleotides to evaluate the mechanisms of BUBU antinociception. European Journal of Pharmacology, 383(1), 29-37. https://doi.org/10.1016/S0014-2999(99)00611-1