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Research ArticleNEUROPHARMACOLOGY

Role of Na+,K+-ATPase in Morphine-Induced Antinociception

Willias Masocha, Gyongyi Horvath, Ahmad Agil, María Ocaña, Esperanza Del Pozo, Margit Szikszay and José M. Baeyens
Journal of Pharmacology and Experimental Therapeutics September 2003, 306 (3) 1122-1128; DOI: https://doi.org/10.1124/jpet.103.052977
Willias Masocha
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Gyongyi Horvath
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Ahmad Agil
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María Ocaña
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Esperanza Del Pozo
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Margit Szikszay
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José M. Baeyens
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Abstract

We evaluated the modulation by Na+,K+-ATPase inhibitors of morphine-induced antinociception in the tail-flick test and [3H]naloxone binding to forebrain membranes. The antinociception induced by morphine (1-32 mg/kg, s.c.) in mice was dose-dependently antagonized by ouabain (1-10 ng/mouse, i.c.v.), which produced a significant shift to the right of the morphine dose-response curve. The i.c.v. administration of three Na+,K+-ATPase inhibitors (ouabain at 0.1-100, digoxin at 1-1,000, and digitoxin at 10-10,000 ng/mouse) dose-dependently antagonized the antinociceptive effect of morphine (4 mg/kg, s.c.) in mice, with the following order of potency: ouabain > digoxin > digitoxin. This effect cannot be explained by any interaction at opioid receptors, since none of these Na+,K+-ATPase inhibitors displaced [3H]naloxone from its binding sites, whereas naloxone did so in a concentration-dependent manner. The antinociception induced by morphine (5 mg/kg, s.c.) in rats was antagonized by the i.c.v. administration of ouabain at 10 ng/rat, whereas it was not significantly modified by intrathecally administered ouabain (10 and 100 ng/rat). These results suggest that the activation of Na+,K+-ATPase plays a role in the supraspinal, but not spinal, antinociceptive effect of morphine.

Footnotes

  • This work was supported by a Hungarian-Spanish Scientific Research grant (17/2001), Spanish Scientific Research Council grants from Comisión Inter-ministerial de Ciencia y Tecnológica (SAF 97-0173) and Junta de Andalucía (CTS-109), and Hungarian Scientific Research grants (OTKA T-34741 and ETT 042/2001).

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • DOI: 10.1124/jpet.103.052977.

  • ABBREVIATIONS: AUC, area under the curve; ANOVA, analysis of variance.

    • Received April 11, 2003.
    • Accepted May 8, 2003.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 306 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 306, Issue 3
1 Sep 2003
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Research ArticleNEUROPHARMACOLOGY

Role of Na+,K+-ATPase in Morphine-Induced Antinociception

Willias Masocha, Gyongyi Horvath, Ahmad Agil, María Ocaña, Esperanza Del Pozo, Margit Szikszay and José M. Baeyens
Journal of Pharmacology and Experimental Therapeutics September 1, 2003, 306 (3) 1122-1128; DOI: https://doi.org/10.1124/jpet.103.052977

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Research ArticleNEUROPHARMACOLOGY

Role of Na+,K+-ATPase in Morphine-Induced Antinociception

Willias Masocha, Gyongyi Horvath, Ahmad Agil, María Ocaña, Esperanza Del Pozo, Margit Szikszay and José M. Baeyens
Journal of Pharmacology and Experimental Therapeutics September 1, 2003, 306 (3) 1122-1128; DOI: https://doi.org/10.1124/jpet.103.052977
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