Toetik Aryani and Tri Kalako and Junaidi Khotib, NIDN. 0022107001 (2008) Mitogen-Activated Protein Kinase Menghambat Perkembangan Toleransi Analgesic Morfina pada Mencit. Majalah Farmasi Airlangga, 6 (1). pp. 5-8. ISSN 0852-1050

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Abstract

Theanalgesic properties and side effects ofmorphine such as tolerance are mediated by the p-opioid receptor Longterm morphine treatment iniates adaptation mechanism like receptor desensitization or internalitation that underlie tolerance. Another adaptation mechanism is the mitogen-activated protein (MAP) kinase cascade. Repeated exposure to morphine activates MAP kinase cascade which elevates the level of MAPkinase extracellularsignaling regulatory protein kinase (ERK 1/2) and MAP kinase p38 causing phosphorylation of many transcriptional factors. In this study, the role of MAP kinase on the development of morphine analgesic tolerance was evaluated by giving inhibitor MAP kinase p38 (SB203580) and inhibitor MAP kinase ERK 1/2 (PD98059). MAP kinase inhibitor injected intrathecally in different doses (0.01 nmol; 0.1 nmol and 10 nmol) to mice before got 10,0 mg/Kg body weight morphine subcutan once daily. Analgesic responses was determined by using hot plate method. The result showed that SB203580 prevented the development of morphine analgesic tolerance at the dose 1.0 nmol (P<0.05) siginificantly different with the control group DMSO 30%. PD98059 also prevented the development of morphine analgesic tolerance at the dose 1.0 nmol (P<0,05) siginificantly different with the control group DMSO 30%. Result ofthisstudies indicated that MAPkinase had a substansial role on inhibiting the development ofmorphine analgesic tolerance

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