Signal transduction underlying carbachol-induced PGE₂ generation and cox-1 mRNA expression of rat brain

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• 作者：Orman ; Betina ; Reina ; Silvia ; Borda ; Enri ; Sterin-Borda ; Leonor
• 关键词：Brain ; Phospholipase C ; Phospholipase A₂ ; PGE₂ ; Calcium/calmodulin ; cox-2 mRNA gene ; cox-1 mRNA gene ; Carbachol ; mAChR
• 刊名：Neuropharmacology
• 出版年：2005
• 期刊代码：33_00283908
• 类别：pha
• 出版时间：April, 2005
• 卷：48
• 期：5
• 页码：757-765
• 文件大小：244 K

摘要

In this paper we have determined the different signal pathways involved in M₁ and M₃ muscarinic acetylcholine receptor (mAChR) dependent stimulation of cyclo-oxygenase 1 (cox-1) mRNA gene expression and PGE₂ production on rat cerebral frontal cortex. Carbachol stimulation of M₁ and M₃ mAChR exerts an increase in cox-1 mRNA gene expression without affecting cox-2 mRNA expression and increased PGE₂ generation. Besides, increased phosphoinositide (PI) turnover and stimulation of nitric oxide synthase (NOS) and cyclic GMP (cGMP) production. Inhibitors of phospholipase A₂ (PLA₂), COX and phospholipase C (PLC), calcium/calmodulin (CaM), NOS and soluble guanylate cyclase prevent the carbachol effect. These results suggest that carbachol-activation of M₁ and M₃ mAChR increased PGE₂ release associated with an increased expression of cox-1 and NO–cGMP production. The mechanism appears to occur directly to PLC stimulation and indirectly to PLA₂ activation. These results may contribute to understand the effects and side effect of non-steroidal anti-inflammatory drugs in patients with cerebral degenerative diseases.