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Indirect role of α2-adrenoreceptors in anti-ulcer effect mechanism of nimesulide in rats

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Abstract

Nimesulide, a non-steroidal, anti-inflammatory drug, produces ulcerogenic effects in adrenalectomized rats but is gastro-protective in intact rats. The objective of this study was to determine whether adrenal gland hormones are involved in the anti-ulcer effects of nimesulide. The results revealed that 100 mg/kg nimesulide produces gastric ulceration in adrenalectomized rats, which is prevented by prednisolone and adrenaline. The anti-ulcer effects of adrenaline and prednisolone in adrenalectomized rats were in turn antagonized by yohimbine, a selective α2-receptor blocker, but not by doxazosine (α1-receptor blocker) or propranolol (β-blocker). Adrenaline prevented the formation of indomethacin-induced ulcers in both adrenalectomized and intact rats, but prednisolone increased the indomethacin-induced ulcerous area in intact rats, whereas it decreased the size of the ulcers in adrenalectomized rats. In addition, prednisolone prevented ulcer formation in intact rats in which the adrenaline concentration had been decreased by metyrosine. These results suggest that glucocorticoids are anti-ulcerogenic in not only adrenalectomized rats but also in intact rats with diminished circulating levels of adrenaline. In the light of these data, the effect of nimesulide on plasma adrenaline concentrations was studied. In comparison to the adrenaline levels found in intact control rats, the administration of nimesulide at doses of 10, 20, 40 and 100 mg/kg decreased adrenaline concentrations by 12.8, 22.6, 30.4, and 58.2%, respectively, without affecting blood corticosterone concentrations. The anti-ulcer effect of nimesulide was observed to be dose-dependent, and the strength of this effect was directly correlated the decreasing concentration of adrenaline. The concentration of adrenaline was decreased by 60.9% in rats treated with 300 mg/kg metyrosine in which prednisolone produced anti-ulcer effects. In summary, we have shown that nimesulide produces its anti-ulcer effect by decreasing endogenous adrenaline concentrations and that glucocorticoids may induce anti-ulcer effects via α2-adrenoreceptors, but not via their own receptors.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Ataturk University, 25240, Erzurum, Turkey

    Halis Suleyman, Zekai Halici, Ahmet Hacimuftuoglu & Fatma Gocer

  2. Department of Pharmacology, Faculty of Pharmacy, Ataturk University, 25240, Erzurum, Turkey

    Elif Cadirci

  3. Department of Biochemistry, Faculty of Medicine, Ataturk University, 25240, Erzurum, Turkey

    Sait Keles

Authors
  1. Halis Suleyman
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  2. Zekai Halici
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  3. Elif Cadirci
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  4. Ahmet Hacimuftuoglu
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  5. Sait Keles
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  6. Fatma Gocer
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Correspondence to Halis Suleyman.

Additional information

This research was conducted in the Laboratory of Pharmacology at Ataturk University, Faculty of Medicine, Department of Pharmacology, 25240 Erzurum/Turkey.

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Suleyman, H., Halici, Z., Cadirci, E. et al. Indirect role of α2-adrenoreceptors in anti-ulcer effect mechanism of nimesulide in rats. Naunyn-Schmied Arch Pharmacol 375, 189–198 (2007). https://doi.org/10.1007/s00210-007-0151-0

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  • DOI: https://doi.org/10.1007/s00210-007-0151-0

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