Role of ATP-sensitive K⁺ channels in the antinociception induced by non-steroidal anti-inflammatory drugs in streptozotocin-diabetic and non-diabetic rats

详细信息	查看全文 | 推荐本文 |

• 作者：Mario I. Ortiz^a ; ^b ; ^{mario_i_ortiz@hotmail.com} ; Gilberto Castañ ; eda-Herná ; ndez^c ; Jeannett A. Izquierdo-Vega^a ; Manuel Sá ; nchez-Gutié ; rrez^a ; Hé ; ctor A. Ponce-Monter^a ; Vinicio Granados-Soto^d
• 关键词：Diclofenac ; Indomethacin ; Lumiracoxib ; Meloxicam ; Metamizol ; K+ channels ; Glibenclamide ; Glipizide ; Streptozotocin-diabetic rat ; Formalin test
• 刊名：Pharmacology Biochemistry and Behavior
• 出版年：2012
• 期刊代码：219_00913057
• 类别：med
• 出版时间：July, 2012
• 卷：102
• 期：1
• 页码：163-169
• 文件大小：459 K

摘要

There is evidence that systemic sulfonylureas block diclofenac-induced antinociception in normal rat, suggesting that diclofenac activates ATP-sensitive K⁺ channels. However, there is no evidence for the systemic interaction between different non-steroidal anti-inflammatory drugs (NSAIDs) and sulfonylureas in streptozotocin (STZ)-diabetic rats. Therefore, this work was undertaken to determine whether two sulfonylureas, glibenclamide and glipizide, have any effect on the systemic antinociception that is induced by diclofenac (30 mg/kg), lumiracoxib (56 mg/kg), meloxicam (30 mg/kg), metamizol (56 mg/kg) and indomethacin (30 mg/kg) using the non-diabetic and STZ-diabetic rat formalin test. Systemic injections of NSAIDs produced dose-dependent antinociception during the second phase of the test in both non-diabetic and STZ-diabetic rats. Systemic pretreatment with glibenclamide (10 mg/kg) and glipizide (10 mg/kg) blocked diclofenac-induced systemic antinociception in the second phase of the test (P < 0.05) in both non-diabetic and STZ-diabetic rats. In contrast, pretreatment with glibenclamide or glipizide did not block lumiracoxib-, meloxicam-, metamizol-, and indomethacin-induced systemic antinociception (P > 0.05) in both groups. Results showed that systemic NSAIDs are able to produce antinociception in STZ-diabetic rats. Likewise, data suggest that diclofenac, but not other NSAIDs, activated K⁺ channels to induce its systemic antinociceptive effect in the non-diabetic and STZ-diabetic rat formalin test.