1. School of pharmaceutical sciences, Universiti Sains Malaysia, Penang, Malaysia 2. Center of Drug Research, Universiti Sains Malaysia, Penang, Malaysia
✉ Corresponding authors: Prof. Lay-Harn Gam; School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia; layharnmy. Associate Professor Dr. Zurina Hassan; zurina_hassanmy; Address: Center of Drug Research, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia.More
Citation:
Basheer M, Hassan Z, Gam LH. Upregulation of Brain's Calcium Binding Proteins in Mitragynine Dependence: A Potential Cellular Mechanism to Addiction. Int J Med Sci 2023; 20(1):102-113. doi:10.7150/ijms.78861. https://www.medsci.org/v20p0102.htm
Background: Mitragyna speciosa Korth or Kratom is widely used traditionally for its medicinal values. The major alkaloid content of kratom leaves is mitragynine, which binds to opioid receptors to give opioid-like effects. This study aimed to analyse the brain proteome of animals that displayed addictive behaviors.
Design and Methods: Six groups (n=6-8) of rats made up of negative control, positive control using morphine (10 mg/kg), and treatment groups at low (1mg/kg) and high doses of mitragynine (30 mg/kg) for 1 and 4 days. The rats' behaviors were evaluated and subsequently the rats' brains were harvested for proteomic analysis that was performed by using 2D gel electrophoresis and LC/MS/MS.
Results: The rats developed physical dependence only on day 4 following morphine and mitragynine (1 and 30mg/kg) treatments. Among the proteins that were up-regulated in treatment groups were four calcium-binding proteins, namely calretinin, F-actin, annexin A3 and beta-centractin.
Conclusions: Upregulation of calretinin acted as low Ca2+ buffering upon the blockage of Ca2+ ion channel by mitragynine in the brain, which subsequently caused a reduction of GABA released and inversely increased the dopamine secretions that contributed to dependence indicators.
Basheer, M., Hassan, Z., Gam, L.H. (2023). Upregulation of Brain's Calcium Binding Proteins in Mitragynine Dependence: A Potential Cellular Mechanism to Addiction. International Journal of Medical Sciences, 20(1), 102-113. https://doi.org/10.7150/ijms.78861.
ACS
Basheer, M.; Hassan, Z.; Gam, L.H. Upregulation of Brain's Calcium Binding Proteins in Mitragynine Dependence: A Potential Cellular Mechanism to Addiction. Int. J. Med. Sci. 2023, 20 (1), 102-113. DOI: 10.7150/ijms.78861.
NLM
Basheer M, Hassan Z, Gam LH. Upregulation of Brain's Calcium Binding Proteins in Mitragynine Dependence: A Potential Cellular Mechanism to Addiction. Int J Med Sci 2023; 20(1):102-113. doi:10.7150/ijms.78861. https://www.medsci.org/v20p0102.htm
CSE
Basheer M, Hassan Z, Gam LH. 2023. Upregulation of Brain's Calcium Binding Proteins in Mitragynine Dependence: A Potential Cellular Mechanism to Addiction. Int J Med Sci. 20(1):102-113.
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