UNIVERSITAS AIRLANGGA



Detail Article

Majalah Farmasi Airlangga (Airlangga Journal of Pharmacy)

ISSN 0852-1050

Vol. 6 / No. 1 / Published : 2008-04

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Original Article :

mitogen-activated protein kinase menghambat perkembangan toleransi analgesik morfina pada mencit

Author :

  1. Toetik Aryani*1
  2. Tri Kaloko*2
  3. Junaidi Khotib*3
  1. Departemen Farmasi Klinis Fakultas Farmasi Universitas Airlangga Surabaya
  2. Departemen Farmasi Klinis Fakultas Farmasi Universitas Airlangga Surabaya
  3. Departemen Farmasi Klinis Fakultas Farmasi Universitas Airlangga Surabaya

Abstract :

The analgesic properties and side effects of morphine such as tolerance are mediated by the μ-opioid receptor. Long-term 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 MAP kinase extracellular signaling 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 1.0 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 of this studies indicated that MAP kinase had a substansial role on inhibiting the development of morphine analgesic tolerance.

Keyword :

morphine, analgesic tolerance, mitogen-activated protein kinase,


References :

Allen, J.W. and Yaksh, T.L,(2004) Assesment of acute thermal nociception in laboratory animals, In : Luo, Z.D. (Eds.), Pain Research: Methods and Protocols, New Jersey : Humana Press,

Cavun, S., Goktalay, G. and Millington, W. R.,(2003) Glycyl-glutamine, an endogenous beta endorphin-derived peptide, inhibits morphine-induced conditioned place preference, tolerance, dependence and withdrawal, : The Journal of Pharmacology and Experimental Therapeutics,

Hill, S. J.,(2006) G-protein coupled receptor : past, present and future : British Journal of Pharmacology

Katzung, B.G,(2005) Basic and Clinical Pharmacology. 9th edition New York : The MacGraw-Hill Companies, Inc





Archive Article

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Volume : 6 / No. : 1 / Pub. : 2008-04
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