Indirect role of alpha2-adrenoreceptors in anti-ulcer effect mechanism of nimesulide in rats
| Autor: | Ahmet Hacimuftuoglu, Halis Suleyman, Elif Cadirci, Fatma Göçer, Sait Keles, Zekai Halici |
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| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty Epinephrine medicine.medical_treatment Prednisolone Indomethacin Metyrosine Propranolol chemistry.chemical_compound Corticosterone Receptors Adrenergic alpha-2 Internal medicine medicine Adrenergic alpha-2 Receptor Agonists Animals Stomach Ulcer Rats Wistar Desoxycorticosterone Pharmacology Sulfonamides Dose-Response Relationship Drug Adrenal gland business.industry Adrenalectomy Anti-Inflammatory Agents Non-Steroidal Doxazosin Yohimbine General Medicine Adrenergic alpha-2 Receptor Antagonists Metyrapone Rats medicine.anatomical_structure Endocrinology alpha-Methyltyrosine chemistry business medicine.drug Nimesulide Hormone |
| Zdroj: | Naunyn-Schmiedeberg's archives of pharmacology. 375(3) |
| ISSN: | 0028-1298 |
| Popis: | 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 alpha(2)-receptor blocker, but not by doxazosine (alpha(1)-receptor blocker) or propranolol (beta-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 alpha(2)-adrenoreceptors, but not via their own receptors. |
| Databáze: | OpenAIRE |
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