Modulation of adenosine-induced responses in the guinea-pig trachea during long-term caffeine treatment: Possible role of epithelium

László Brugós, R. Gesztelyi, Judit Zsuga, Ágnes Cseppento, Ilona Benko, Zoltán Galajda, G. Deák, S. Sipka, Tamás Roszer, Péter Kovács, Mária Szilasi, I. Édes, András József Szentmiklósi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The responses to adenosine were studied on isolated, methacholine- precontracted tracheal strips of guinea pigs in the course of long-term caffeine or solvent treatment. Guinea pigs were fed caffeine for 10 weeks (average serum caffeine concentration: 39.1 ± 3.9 μM). In epithelium-intact tracheal preparations (EITPs), sensititization to adenosine-induced relaxation (AIR) developed. It attained a maximum in week 1 of caffeine treatment, and then its level diminished and disappeared completely by weeks 4 - 6. In epithelium-denuded tracheal preparations (EDTPs), an increase in the sensitivity to adenosine was observed from week 1 to week 10 (a 4 - 6-fold reduction in EC50). Use of a coaxial bioassay system confirmed the role of epithelium in this process. The enhancement of the AIR of the EITPs was not modified by inhibitors of cyclooxygenase and lipoxygenase. Following depletion of the neuropeptides by acute capsaicin pretreatment, the AIR of the EITPs was strongly enhanced after caffeine treatment for 6 weeks. In chronically caffeine-treated EITPs, the inhibition of neutral endopeptidase led to dramatic reduction of the AIR. On the basis of the results by inhibiting nitric oxide synthase, it can be supposed that nitric oxide released from EITPs of long-lasting caffeine-treated animals operated as a constrictor agent. Our results show that chronic caffeine treatment gives rise to an initial sensitization to adenosine of the EITPs, this being followed by the development of a specific adaptive process in the epithelial cells, which counterbalances the increased tracheal sensitivity to adenosine.

Original languageEnglish
Pages (from-to)279-290
Number of pages12
JournalJournal of Pharmacological Sciences
Volume105
Issue number3
DOIs
Publication statusPublished - 2007

Fingerprint

Caffeine
Trachea
Adenosine
Guinea Pigs
Epithelium
Neprilysin
Lipoxygenase Inhibitors
Cyclooxygenase Inhibitors
Methacholine Chloride
Capsaicin
Neuropeptides
Nitric Oxide Synthase
Biological Assay
Nitric Oxide
Epithelial Cells
Serum

Keywords

  • Adenosine
  • Chronic caffeine treatment
  • Epithelium
  • Trachea

ASJC Scopus subject areas

  • Pharmacology

Cite this

Modulation of adenosine-induced responses in the guinea-pig trachea during long-term caffeine treatment : Possible role of epithelium. / Brugós, László; Gesztelyi, R.; Zsuga, Judit; Cseppento, Ágnes; Benko, Ilona; Galajda, Zoltán; Deák, G.; Sipka, S.; Roszer, Tamás; Kovács, Péter; Szilasi, Mária; Édes, I.; Szentmiklósi, András József.

In: Journal of Pharmacological Sciences, Vol. 105, No. 3, 2007, p. 279-290.

Research output: Contribution to journalArticle

Brugós, László ; Gesztelyi, R. ; Zsuga, Judit ; Cseppento, Ágnes ; Benko, Ilona ; Galajda, Zoltán ; Deák, G. ; Sipka, S. ; Roszer, Tamás ; Kovács, Péter ; Szilasi, Mária ; Édes, I. ; Szentmiklósi, András József. / Modulation of adenosine-induced responses in the guinea-pig trachea during long-term caffeine treatment : Possible role of epithelium. In: Journal of Pharmacological Sciences. 2007 ; Vol. 105, No. 3. pp. 279-290.
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abstract = "The responses to adenosine were studied on isolated, methacholine- precontracted tracheal strips of guinea pigs in the course of long-term caffeine or solvent treatment. Guinea pigs were fed caffeine for 10 weeks (average serum caffeine concentration: 39.1 ± 3.9 μM). In epithelium-intact tracheal preparations (EITPs), sensititization to adenosine-induced relaxation (AIR) developed. It attained a maximum in week 1 of caffeine treatment, and then its level diminished and disappeared completely by weeks 4 - 6. In epithelium-denuded tracheal preparations (EDTPs), an increase in the sensitivity to adenosine was observed from week 1 to week 10 (a 4 - 6-fold reduction in EC50). Use of a coaxial bioassay system confirmed the role of epithelium in this process. The enhancement of the AIR of the EITPs was not modified by inhibitors of cyclooxygenase and lipoxygenase. Following depletion of the neuropeptides by acute capsaicin pretreatment, the AIR of the EITPs was strongly enhanced after caffeine treatment for 6 weeks. In chronically caffeine-treated EITPs, the inhibition of neutral endopeptidase led to dramatic reduction of the AIR. On the basis of the results by inhibiting nitric oxide synthase, it can be supposed that nitric oxide released from EITPs of long-lasting caffeine-treated animals operated as a constrictor agent. Our results show that chronic caffeine treatment gives rise to an initial sensitization to adenosine of the EITPs, this being followed by the development of a specific adaptive process in the epithelial cells, which counterbalances the increased tracheal sensitivity to adenosine.",
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T2 - Possible role of epithelium

AU - Brugós, László

AU - Gesztelyi, R.

AU - Zsuga, Judit

AU - Cseppento, Ágnes

AU - Benko, Ilona

AU - Galajda, Zoltán

AU - Deák, G.

AU - Sipka, S.

AU - Roszer, Tamás

AU - Kovács, Péter

AU - Szilasi, Mária

AU - Édes, I.

AU - Szentmiklósi, András József

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N2 - The responses to adenosine were studied on isolated, methacholine- precontracted tracheal strips of guinea pigs in the course of long-term caffeine or solvent treatment. Guinea pigs were fed caffeine for 10 weeks (average serum caffeine concentration: 39.1 ± 3.9 μM). In epithelium-intact tracheal preparations (EITPs), sensititization to adenosine-induced relaxation (AIR) developed. It attained a maximum in week 1 of caffeine treatment, and then its level diminished and disappeared completely by weeks 4 - 6. In epithelium-denuded tracheal preparations (EDTPs), an increase in the sensitivity to adenosine was observed from week 1 to week 10 (a 4 - 6-fold reduction in EC50). Use of a coaxial bioassay system confirmed the role of epithelium in this process. The enhancement of the AIR of the EITPs was not modified by inhibitors of cyclooxygenase and lipoxygenase. Following depletion of the neuropeptides by acute capsaicin pretreatment, the AIR of the EITPs was strongly enhanced after caffeine treatment for 6 weeks. In chronically caffeine-treated EITPs, the inhibition of neutral endopeptidase led to dramatic reduction of the AIR. On the basis of the results by inhibiting nitric oxide synthase, it can be supposed that nitric oxide released from EITPs of long-lasting caffeine-treated animals operated as a constrictor agent. Our results show that chronic caffeine treatment gives rise to an initial sensitization to adenosine of the EITPs, this being followed by the development of a specific adaptive process in the epithelial cells, which counterbalances the increased tracheal sensitivity to adenosine.

AB - The responses to adenosine were studied on isolated, methacholine- precontracted tracheal strips of guinea pigs in the course of long-term caffeine or solvent treatment. Guinea pigs were fed caffeine for 10 weeks (average serum caffeine concentration: 39.1 ± 3.9 μM). In epithelium-intact tracheal preparations (EITPs), sensititization to adenosine-induced relaxation (AIR) developed. It attained a maximum in week 1 of caffeine treatment, and then its level diminished and disappeared completely by weeks 4 - 6. In epithelium-denuded tracheal preparations (EDTPs), an increase in the sensitivity to adenosine was observed from week 1 to week 10 (a 4 - 6-fold reduction in EC50). Use of a coaxial bioassay system confirmed the role of epithelium in this process. The enhancement of the AIR of the EITPs was not modified by inhibitors of cyclooxygenase and lipoxygenase. Following depletion of the neuropeptides by acute capsaicin pretreatment, the AIR of the EITPs was strongly enhanced after caffeine treatment for 6 weeks. In chronically caffeine-treated EITPs, the inhibition of neutral endopeptidase led to dramatic reduction of the AIR. On the basis of the results by inhibiting nitric oxide synthase, it can be supposed that nitric oxide released from EITPs of long-lasting caffeine-treated animals operated as a constrictor agent. Our results show that chronic caffeine treatment gives rise to an initial sensitization to adenosine of the EITPs, this being followed by the development of a specific adaptive process in the epithelial cells, which counterbalances the increased tracheal sensitivity to adenosine.

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