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Central Nervous System Agents in Medicinal Chemistry

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ISSN (Print): 1871-5249
ISSN (Online): 1875-6166

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Research Article

Erythroxylum cuneatum Prevented Cellular Adaptation in Morphineinduced Neuroblastoma Cells

Author(s): Noor Azuin Suliman, Mohamad Aris Mohd Moklas*, Che Norma Mat Taib, Mohamad Taufik Hidayat Baharuldin and Musa Samaila Chiroma

Volume 22, Issue 2, 2022

Published on: 15 July, 2022

Page: [108 - 117] Pages: 10

DOI: 10.2174/1871524922666220516151121

Price: $65

Abstract

Background: Chronic morphine stimulates prolonged stimulation of opioid receptors, especially μ-opioid subtype (MOR), which in turn signals cellular adaptation. However, the sudden termination of the use of morphine after chronic intake causes the withdrawal syndrome.

Objectives: Hence, this study was designed to find an alternative treatment for morphine withdrawal using the alkaloid leaf extract of Erythroxylum cuneatum (E. cuneatum) for the treatment of morphine-exposed neuroblastoma cell lines.

Methods: SK-N-SH, a commercialised neuroblastoma cell line, was used in two separate study designs; the antagonistic and pre-treatment of morphine. The antagonistic treatment was conducted through concurrent exposure of the cells to morphine and E. cuneatum or morphine and methadone for 24 hrs. The pre-treatment design was carried out by exposing the cells to morphine for 24 hrs, followed by 24 hrs exposure to E. cuneatum or methadone. The cytosolic fraction was collected and assessed for proteins expression involved in cellular adaptation, including mitogen-activated protein (MAP)/extracellular signal-regulated (ERK) kinase 1/2 (MEK 1/2), extracellular signalregulated kinase 2 (ERK 2), cAMP-dependent protein kinase (PKA) and protein kinases C (PKC).

Results: The antagonistic treatment showed the normal level of MEK 1/2, ERK 2, PKA and PKC by the combination treatment of morphine and E. cuneatum, comparable to the combination of morphine and methadone. Neuroblastoma cells exposed to morphine pre-treatment expressed a high level of MEK 1/2, ERK 2, PKA and PKC, while the treatments with E. cuneatum and methadone normalised the expression of the cellular adaptation proteins.

Conclusion: E. cuneatum exerted anti-addiction properties by lowering the levels of cellular adaptation proteins it’s effects is comparable to that of methadone (an established anti-addiction drug).

Keywords: Erythroxylum cuneatum, chronic morphine, cellular adaptation, anti-addiction, methadone, μ-opioid receptor, human neuroblastoma cell line (SK-N-SH).

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[1]
Anand, K.J.; Willson, D.F.; Berger, J.; Harrison, R.; Meert, K.L.; Zimmerman, J.; Carcillo, J.; Newth, C.J.; Prodhan, P.; Dean, J.M.; Nicholson, C. Tolerance and withdrawal from prolonged opioid use in critically ill children. Pediatrics, 2010, 125(5), e1208-e1225.
[http://dx.doi.org/10.1542/peds.2009-0489] [PMID: 20403936]
[2]
McClung, C.A.; Nestler, E.J.; Zachariou, V. Regulation of gene expression by chronic morphine and morphine withdrawal in the locus ceruleus and ventral tegmental area. J. Neurosci., 2005, 25(25), 6005-6015.
[http://dx.doi.org/10.1523/JNEUROSCI.0062-05.2005] [PMID: 15976090]
[3]
Williams, J.T.; Christie, M.J.; Manzoni, O. Cellular and synaptic adaptations mediating opioid dependence. Physiol. Rev., 2001, 81(1), 299-343.
[http://dx.doi.org/10.1152/physrev.2001.81.1.299] [PMID: 11152760]
[4]
Nakai, T.; Hayashi, M.; Ichihara, K.; Wakabayashi, H.; Hoshi, K. Noradrenaline release in rat locus coeruleus is regulated by both opioid and α(2) -adrenoceptors. Pharmacol. Res., 2002, 45(5), 407-412.
[http://dx.doi.org/10.1006/phrs.2002.0962] [PMID: 12123629]
[5]
Xie, K.; Colgan, L.A.; Dao, M.T.; Muntean, B.S.; Sutton, L.P.; Orlandi, C.; Boye, S.L.; Boye, S.E.; Shih, C.C.; Li, Y.; Xu, B.; Smith, R.G.; Yasuda, R.; Martemyanov, K.A. NF1 is a direct G protein effector essential for opioid signaling to ras in the striatum. Curr. Biol., 2016, 26(22), 2992-3003.
[http://dx.doi.org/10.1016/j.cub.2016.09.010] [PMID: 27773571]
[6]
Monday, H.R.; Younts, T.J.; Castillo, P.E. Long-term plasticity of neurotransmitter release: Emerging mechanisms and contributions to brain function and disease. Annu. Rev. Neurosci., 2018, 41(1), 299-322.
[http://dx.doi.org/10.1146/annurev-neuro-080317-062155] [PMID: 29709205]
[7]
Cerezo, M.; Milanés, M.V.; Laorden, M.L. Alterations in protein kinase A and different protein kinase C isoforms in the heart during morphine withdrawal. Eur. J. Pharmacol., 2005, 522(1-3), 9-19.
[http://dx.doi.org/10.1016/j.ejphar.2005.08.025] [PMID: 16202991]
[8]
Tokuyama, S.; Feng, Y.; Wakabayashi, H.; Ho, I.K. Possible involvement of protein kinases in physical dependence on opioids: Studies using protein kinase inhibitors, H-7 and H-8. Eur. J. Pharmacol., 1995, 284(1-2), 101-107.
[http://dx.doi.org/10.1016/0014-2999(95)00370-Z] [PMID: 8549612]
[9]
Cao, J.L.; Liu, H.L.; Wang, J.K.; Zeng, Y.M. Cross talk between nitric oxide and ERK1/2 signaling pathway in the spinal cord mediates naloxone-precipitated withdrawal in morphine-dependent rats. Neuropharmacology, 2006, 51(2), 315-326.
[http://dx.doi.org/10.1016/j.neuropharm.2006.03.028] [PMID: 16712881]
[10]
Ali, N.; Aziz, S.A.; Nordin, S.; Mi, N.C.; Abdullah, N.; Paranthaman, V.; Mahmud, M.; Yee, A.; Danaee, M. Evaluation of methadone treatment in Malaysia: Findings from the malaysian methadone treatment outcome study (MyTOS). Subst. Use Misuse, 2018, 53(2), 239-248.
[http://dx.doi.org/10.1080/10826084.2017.1385630] [PMID: 29116878]
[11]
Abadinsky, H. Drug use and abuse; A comprehensive introduction, 7th ed; WADSWORTH: Belmont, U.S.A., 2010, pp. 224-290.
[12]
Sadovsky, R. Public health issue: Methadone maintenance therapy. Am. Fam. Physician, 2000, 62(2), 428-432.
[13]
Leavitt, S.B. Methadone dosing & safety in the treatment of opioid addiction. In Addiction Treatment Forum, 12(2), 1-8.http://citeseerx.ist.psu.edu Available from:
[14]
Suliman, N.A.; Mohd Moklas, M.A.; Mat Taib, C.N.; Adenan, M.I.; Hidayat Baharuldin, M.T.; Basir, R.; Amom, Z. Morphine antidependence of Erythroxylum cuneatum (Miq.) Kurz in neurotransmission processes In Vitro. Evid. Based Complement. Alternat. Med., 2016, 2016, 3517209.
[http://dx.doi.org/10.1155/2016/3517209] [PMID: 27974903]
[15]
Zaki, M.A.A.; Moklas, M.A.M.; Baharuldin, M.T.H.; Adenan, M.I.; Jamil, M.F.A.; Taib, C.N.M.J. In vitro study on anti-withdrawal properties of Erythroxylum cuneatum (Mig.) Kurz leaf alkaloid extract. Nat Prod Pharmaco Res, 2017, 1(1), 20-24.
[16]
Al-Hasani, R.; Bruchas, M.R. Molecular mechanisms of opioid receptor-dependent signaling and behavior. Anesthesiology, 2011, 115(6), 1363-1381.
[http://dx.doi.org/10.1097/ALN.0b013e318238bba6] [PMID: 22020140]
[17]
Lin, X.; Wang, Q.; Ji, J.; Yu, L.C. Role of MEK-ERK pathway in morphine-induced conditioned place preference in ventral tegmental area of rats. J. Neurosci. Res., 2010, 88(7), 1595-1604.
[http://dx.doi.org/10.1002/jnr.22326] [PMID: 20091775]
[18]
Lefkowitz, R.J. G protein-coupled receptors. III. New roles for receptor kinases and β-arrestins in receptor signaling and desensitization. J. Biol. Chem., 1998, 273(30), 18677-18680.
[http://dx.doi.org/10.1074/jbc.273.30.18677] [PMID: 9668034]
[19]
Jamil, M.F.A.; Subki, M.F.M.; Lan, T.M.; Majid, M.I.A.; Adenan, M.I. The effect of mitragynine on cAMP formation and mRNA expression of mu-opioid receptors mediated by chronic morphine treatment in SK-N-SH neuroblastoma cell. J. Ethnopharmacol., 2013, 148(1), 135-143.
[http://dx.doi.org/10.1016/j.jep.2013.03.078] [PMID: 23608241]
[20]
Chao, J.; Nestler, E.J. Molecular neurobiology of drug addiction. Annu. Rev. Med., 2004, 55(1), 113-132.
[http://dx.doi.org/10.1146/annurev.med.55.091902.103730] [PMID: 14746512]
[21]
Cao, J.L.; He, J.H.; Ding, H.L.; Zeng, Y.M. Activation of the spinal ERK signaling pathway contributes naloxone-precipitated withdrawal in morphine-dependent rats. Pain, 2005, 118(3), 336-349.
[http://dx.doi.org/10.1016/j.pain.2005.09.006] [PMID: 16289800]
[22]
Adams, J.P.; Sweatt, J.D. Molecular psychology: Roles for the ERK MAP kinase cascade in memory. Annu. Rev. Pharmacol. Toxicol., 2002, 42(1), 135-163.
[http://dx.doi.org/10.1146/annurev.pharmtox.42.082701.145401] [PMID: 11807168]
[23]
Cowan, K.J.; Storey, K.B. Mitogen-activated protein kinases: New signaling pathways functioning in cellular responses to environmental stress. J. Exp. Biol., 2003, 206(Pt 7), 1107-1115.
[http://dx.doi.org/10.1242/jeb.00220] [PMID: 12604570]
[24]
Núñez, C.; Laorden, M.L.; Milanés, M.V. Regulation of serine (Ser)-31 and Ser40 tyrosine hydroxylase phosphorylation during morphine withdrawal in the hypothalamic paraventricular nucleus and nucleus tractus solitarius-A2 cell group: Role of ERK1/2. Endocrinology, 2007, 148(12), 5780-5793.
[http://dx.doi.org/10.1210/en.2007-0510] [PMID: 17823252]
[25]
Tso, P.H.; Wong, Y.H. Role of extracellular signal-regulated kinases in opioid-induced adenylyl cyclase superactivation in human embryonic kidney 293 cells. Neurosci. Lett., 2001, 316(1), 13-16.
[http://dx.doi.org/10.1016/S0304-3940(01)02340-0] [PMID: 11720767]
[26]
Nestler, E.J. Historical review: Molecular and cellular mechanisms of opiate and cocaine addiction. Trends Pharmacol. Sci., 2004, 25(4), 210-218.
[http://dx.doi.org/10.1016/j.tips.2004.02.005] [PMID: 15063085]
[27]
Liu, J.G.; Anand, K.J.S. Protein kinases modulate the cellular adaptations associated with opioid tolerance and dependence. Brain Res. Brain Res. Rev., 2001, 38(1-2), 1-19.
[http://dx.doi.org/10.1016/S0165-0173(01)00057-1] [PMID: 11750924]
[28]
Belcheva, M.M.; Vogel, Z.; Ignatova, E.; Avidor-Reiss, T.; Zippel, R.; Levy, R.; Young, E.C.; Barg, J.; Coscia, C.J. Opioid modulation of extracellular signal-regulated protein kinase activity is ras-dependent and involves Gbetagamma subunits. J. Neurochem., 1998, 70(2), 635-645.
[http://dx.doi.org/10.1046/j.1471-4159.1998.70020635.x] [PMID: 9453557]
[29]
Miyatake, M.; Rubinstein, T.J.; McLennan, G.P.; Belcheva, M.M.; Coscia, C.J. Inhibition of EGF-induced ERK/MAP kinase-mediated astrocyte proliferation by μ opioids: Integration of G protein and β-arrestin 2-dependent pathways. J. Neurochem., 2009, 110(2), 662-674.
[http://dx.doi.org/10.1111/j.1471-4159.2009.06156.x] [PMID: 19457093]
[30]
Belcheva, M.M.; Clark, A.L.; Haas, P.D.; Serna, J.S.; Hahn, J.W.; Kiss, A.; Coscia, C.J. μ and κ opioid receptors activate ERK/MAPK via different protein kinase C isoforms and secondary messengers in astrocytes. J. Biol. Chem., 2005, 280(30), 27662-27669.
[http://dx.doi.org/10.1074/jbc.M502593200] [PMID: 15944153]
[31]
Asensio, V.J.; Miralles, A.; García-Sevilla, J.A. Stimulation of mitogen-activated protein kinase kinases (MEK1/2) by μ-, δ- and κ-opioid receptor agonists in the rat brain: Regulation by chronic morphine and opioid withdrawal. Eur. J. Pharmacol., 2006, 539(1-2), 49-56.
[http://dx.doi.org/10.1016/j.ejphar.2006.04.001] [PMID: 16678156]
[32]
Macey, T.A.; Bobeck, E.N.; Hegarty, D.M.; Aicher, S.A.; Ingram, S.L.; Morgan, M.M. Extracellular signal-regulated kinase 1/2 activation counteracts morphine tolerance in the periaqueductal gray of the rat. J. Pharmacol. Exp. Ther., 2009, 331(2), 412-418.
[http://dx.doi.org/10.1124/jpet.109.152157] [PMID: 19684256]
[33]
Hofford, R.S.; Hodgson, S.R.; Roberts, K.W.; Bryant, C.D.; Evans, C.J.; Eitan, S. Extracellular signal-regulated kinase activation in the amygdala mediates elevated plus maze behavior during opioid withdrawal. Behav. Pharmacol., 2009, 20(7), 576-583.
[http://dx.doi.org/10.1097/FBP.0b013e32832ec57e] [PMID: 19738463]
[34]
Ferguson, S.S. Evolving concepts in G protein-coupled receptor endocytosis: The role in receptor desensitization and signaling. Pharmacol. Rev., 2001, 53(1), 1-24.
[PMID: 11171937]
[35]
Hausdorff, W.P.; Caron, M.G.; Lefkowitz, R.J. Turning off the signal: Desensitization of beta-adrenergic receptor function. FASEB J., 1990, 4(11), 2881-2889.
[http://dx.doi.org/10.1096/fasebj.4.11.2165947] [PMID: 2165947]
[36]
Smart, D.; Lambert, D.G. Desensitization of the μ-opioid activation of phospholipase C in SH-SY5Y cells: The role of protein kinases C and A and Ca(2+)-activated K+ currents. Br. J. Pharmacol., 1995, 116(6), 2655-2660.
[http://dx.doi.org/10.1111/j.1476-5381.1995.tb17222.x] [PMID: 8590985]
[37]
Fundytus, M.E.; Coderre, T.J. Chronic inhibition of intracellular Ca2+ release or protein kinase C activation significantly reduces the development of morphine dependence. Eur. J. Pharmacol., 1996, 300(3), 173-181.
[http://dx.doi.org/10.1016/0014-2999(95)00871-3] [PMID: 8739205]
[38]
Narita, M.; Makimura, M.; Feng, Y.; Hoskins, B.; Ho, I.K. Influence of chronic morphine treatment on protein kinase C activity: Comparison with butorphanol and implication for opioid tolerance. Brain Res., 1994, 650(1), 175-179.
[http://dx.doi.org/10.1016/0006-8993(94)90224-0] [PMID: 7953672]
[39]
Mayer, D.J.; Mao, J.; Price, D.D. The development of morphine tolerance and dependence is associated with translocation of protein kinase C. Pain, 1995, 61(3), 365-374.
[http://dx.doi.org/10.1016/0304-3959(95)00023-L] [PMID: 7478679]
[40]
Sweitzer, S.M.; Wong, S.M.; Tjolsen, A.; Allen, C.P.; Mochly-Rosen, D.; Kendig, J.J. Exaggerated nociceptive responses on morphine withdrawal: Roles of protein kinase C ε and γ. Pain, 2004, 110(1-2), 281-289.
[http://dx.doi.org/10.1016/j.pain.2004.04.004] [PMID: 15275778]

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