Lithium reverses the effect of opioids on eNOS/nitric oxide pathway in human umbilical vein endothelial cells.
Analgesics, Opioid
/ metabolism
Cell Survival
/ drug effects
Cyclic AMP
/ metabolism
Drug Tolerance
/ genetics
Glycogen Synthase Kinase 3 beta
/ antagonists & inhibitors
Human Umbilical Vein Endothelial Cells
/ drug effects
Humans
Immunohistochemistry
Lithium Chloride
/ pharmacology
Methadone
/ administration & dosage
Morphine
/ administration & dosage
Nitric Oxide
/ metabolism
Nitric Oxide Synthase Type III
/ genetics
Phosphorylation
Signal Transduction
/ drug effects
Huvecs
Lithium
Methadone
Morphine
Tolerance
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
10
06
2020
accepted:
25
08
2020
pubmed:
6
9
2020
medline:
4
6
2021
entrez:
5
9
2020
Statut:
ppublish
Résumé
The main challenge of pain management with opioids is development of acute and chronic analgesic tolerance. Several studies on neuronal cells have focused on the molecular mechanisms involved in tolerance such as cyclic AMP (cAMP) activation, and nitric oxide (NO) pathway. However, the effects of opioids on non-neuronal cells and tolerance development have been poorly investigated. Lithium chloride is a glycogen synthase kinase 3β (GSK-3β) inhibitor and exert its effects through modulation of nitric oxide pathway. In this study we examined the effect of lithium on acute/chronic morphine and methadone administration in endothelial cells which express mu opioid receptors. Human umbilical vein endothelial cells (HUVECs) were treated with different doses of morphine, methadone, and lithium for six and 48 h. Then we evaluated cell viability, nitrite and cyclic AMP levels, as well as the expression of endothelial nitric oxide synthase (eNOS) protein using Immunocytochemistry (ICC) assay and phosphorylated GSK-3β enzyme by western blot analysis in cells. Both chronic morphine and methadone treatment increased NO level and eNOS expression in HUVECs. Morphine induced cAMP overproduction after 48 h exposure with cells. Lithium pretreatment (10 mM) in both morphine and methadone received groups significantly reduced nitrite and cAMP levels as well as eNOS expression as compared to the control. The decreased amount of phospho GSK-3β due to the opioid exposure was increased following lithium treatment. Tolerance like pattern may occur in non-neuronal cells with opioid receptors and this study clearly revealed the attenuation of morphine and methadone tolerance like behavior by lithium treatment in HUVECs.
Identifiants
pubmed: 32888132
doi: 10.1007/s11033-020-05740-9
pii: 10.1007/s11033-020-05740-9
doi:
Substances chimiques
Analgesics, Opioid
0
Nitric Oxide
31C4KY9ESH
Morphine
76I7G6D29C
Cyclic AMP
E0399OZS9N
NOS3 protein, human
EC 1.14.13.39
Nitric Oxide Synthase Type III
EC 1.14.13.39
GSK3B protein, human
EC 2.7.11.1
Glycogen Synthase Kinase 3 beta
EC 2.7.11.1
Lithium Chloride
G4962QA067
Methadone
UC6VBE7V1Z
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6829-6840Subventions
Organisme : Tehran University of Medical Sciences and Health Services
ID : 97-03-30-39415
Références
Borgland SL (2001) Acute opioid receptor desensitization and tolerance: is there a link? Clin Exp Pharmacol Physiol 28(3):147–154
pubmed: 11207668
Williams JT, Ingram SL, Henderson G, Chavkin C, von Zastrow M, Schulz S, Koch T, Evans CJ, Christie MJ (2013) Regulation of µ-opioid receptors: desensitization, phosphorylation, internalization, and tolerance. Pharmacol Rev 65(1):223–254
pubmed: 23321159
pmcid: 3565916
Al-Hasani R, Bruchas MR (2011) Molecular mechanisms of opioid receptor-dependent signaling and behavior. Anesthesiology 115(6):1363–1381
pubmed: 22020140
pmcid: 3698859
Toda N, Kishioka S, Hatano Y, Toda H (2009) Modulation of opioid actions by nitric oxide signaling. Anesthesiology 110(1):166–181
pubmed: 19104184
Beurel E, Grieco SF, Jope RS (2015) Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases. Pharmacol Ther 148:114–131
pubmed: 25435019
Jope RS, Yuskaitis CJ, Beurel E (2007) Glycogen synthase kinase-3 (GSK3): inflammation, diseases, and therapeutics. Neurochem Res 32(4–5):577–595
pubmed: 16944320
Parkitna JR, Obara I, Wawrzczak-Bargiela A, Makuch W, Przewlocka B, Przewlocki R (2006) Effects of glycogen synthase kinase 3β and cyclin-dependent kinase 5 inhibitors on morphine-induced analgesia and tolerance in rats. J Pharmacol Exp Ther 319(2):832–839
pubmed: 16902054
Liao W-W, Tsai S-Y, Liao C-C, Chen K-B, Yeh G-C, Chen J-Y, Wen Y-R (2014) Coadministration of glycogen-synthase kinase 3 inhibitor with morphine attenuates chronic morphine-induced analgesic tolerance and withdrawal syndrome. J Chin Med Assoc 77(1):31–37
pubmed: 24176578
Klein PS, Melton DA (1996) A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci 93(16):8455–8459
pubmed: 8710892
Stambolic V, Ruel L, Woodgett JR (1996) Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells. Curr Biol 6(12):1664–1669
pubmed: 8994831
Chalecka-Franaszek E, Chuang D-M (1999) Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons. Proc Natl Acad Sci 96(15):8745–8750
pubmed: 10411946
Harvey B, Carstens M, Taljaard J (1990) Lithium modulation of cortical cyclic nucleotides: evidence for the Yin-Yang hypothesis. Eur J Pharmacol 175(2):129–136
pubmed: 2155792
Ghasemi M, Dehpour AR (2011) The NMDA receptor/nitric oxide pathway: a target for the therapeutic and toxic effects of lithium. Trends Pharmacol Sci 32(7):420–434
pubmed: 21492946
Dehpour A, Farsam H, Azizabadi-Farahani M (1995) Inhibition of the morphine withdrawal syndrome and the development of physical dependence by lithium in mice. Neuropharmacology 34(1):115–121
pubmed: 7623960
Alborzi A, Mehr SE, Rezania F, Badakhshan S, Mombeini T, Shafaroodi H, Moezi L, Ravan MN, Sharifian M, Dehpour AR (2006) The effect of lithium chloride on morphine-induced tolerance and dependence in isolated guinea pig ileum. Eur J Pharmacol 545(2–3):123–128
pubmed: 16904101
Allouche S, Noble F, Marie N (2014) Opioid receptor desensitization: mechanisms and its link to tolerance. Front Pharmacol 5:280
pubmed: 25566076
pmcid: 4270172
Stefano GB, Hartman A, Bilfinger TV, Magazine HI, Liu Y, Casares F, Goligorsky MS (1995) Presence of the μ3 opiate receptor in endothelial cells coupling to nitric oxide production and vasodilation. J Biol Chem 270(51):30290–30293
pubmed: 8530450
Cadet P, Mantione KJ, Bilfinger TV, Stefano GB (2004) Differential expression of the human mu opiate receptor from different primary vascular endothelial cells. Med Sci Monit 10(10):BR351–BR355
pubmed: 15448587
Yamamizu K, Furuta S, Hamada Y, Yamashita A, Kuzumaki N, Narita M, Doi K, Katayama S, Nagase H, Yamashita JK (2013) к Opioids inhibit tumor angiogenesis by suppressing VEGF signaling. Sci Rep 3:3213
pubmed: 24225480
pmcid: 3827603
Wen H, Lu Y, Yao H, Buch S (2011) Morphine induces expression of platelet-derived growth factor in human brain microvascular endothelial cells: implication for vascular permeability. PLoS ONE 6(6):e21707
pubmed: 21738771
pmcid: 3125302
Pan Y, Sun X, Jiang L, Hu L, Han Y, Qian C, Song C, Qian Y, Liu W (2016) Metformin reduces morphine tolerance by inhibiting microglial-mediated neuroinflammation. J Neuroinflammation 13(1):294
pubmed: 27855689
pmcid: 5114746
Davis AM, Inturrisi CE (1999) d-Methadone blocks morphine tolerance andN-methyl-D-aspartate-induced hyperalgesia. J Pharmacol Exp Ther 289(2):1048–1053
pubmed: 10215686
Posa L, Accarie A, Noble F, Marie N (2015) Methadone reverses analgesic tolerance induced by morphine pretreatment. Int J Neuropsychopharmacol 19(7):pyv108
pmcid: 4966270
Hsiao P-N, Chang M-C, Cheng W-F, Chen C-A, Lin H-W, Hsieh C-Y, Sun W-Z (2009) Morphine induces apoptosis of human endothelial cells through nitric oxide and reactive oxygen species pathways. Toxicology 256(1–2):83–91
pubmed: 19070643
Gupta K, Kshirsagar S, Chang L, Schwartz R, Law P-Y, Yee D, Hebbel RP (2002) Morphine stimulates angiogenesis by activating proangiogenic and survival-promoting signaling and promotes breast tumor growth. Can Res 62(15):4491–4498
Polakiewicz RD, Schieferl SM, Dorner LF, Kansra V, Comb MJ (1998) A mitogen-activated protein kinase pathway is required for μ-opioid receptor desensitization. J Biol Chem 273(20):12402–12406
pubmed: 9575195
Zeilbeck LF, Müller B, Knobloch V, Tamm ER, Ohlmann A (2014) Differential angiogenic properties of lithium chloride in vitro and in vivo. PLoS ONE 9(4):e95546
pubmed: 24751879
pmcid: 3994089
Dong B-T, Tu G-J, Han Y-X, Chen Y (2015) Lithium enhanced cell proliferation and differentiation of mesenchymal stem cells to neural cells in rat spinal cord. Int J Clin Exp Pathol 8(3):2473
pubmed: 26045753
pmcid: 4440062
Sahebgharani M, Nejati M, Sepehrizadeh Z, Khorramizadeh MR, Bahroloumi M, Bozchlou SH, Esmaeili J (2007) Lithium chloride protects PC12 pheochromocytoma cell line against morphine induced apoptosis. Toxicol Lett 172:S71
Förstermann U, Pollock JS, Schmidt H, Heller M, Murad F (1991) Calmodulin-dependent endothelium-derived relaxing factor/nitric oxide synthase activity is present in the particulate and cytosolic fractions of bovine aortic endothelial cells. Proc Natl Acad Sci 88(5):1788–1792
pubmed: 1705708
Khan MI, Ostadhadi S, Mumtaz F, Momeny M, Moghaddaskho F, Hassanipour M, Ejtemaei-Mehr S, Dehpour AR (2017) Thalidomide attenuates the development and expression of antinociceptive tolerance to μ-opioid agonist morphine through l-arginine-iNOS and nitric oxide pathway. Biomed Pharmacother 85:493–502
pubmed: 27899254
Rashki A, Mumtaz F, Jazayeri F, Shadboorestan A, Esmaeili J, Mehr SE, Ghahremani MH, Dehpour AR (2018) Cyclosporin A attenuating morphine tolerance through inhibiting NO/ERK signaling pathway in human glioblastoma cell line: the involvement of calcineurin. EXCLI J 17:1137
pubmed: 30713473
pmcid: 6341459
Shirooie S, Sahebgharani M, Esmaeili J, Dehpour AR (2019) In vitro evaluation of effects of metformin on morphine and methadone tolerance through mammalian target of rapamycin signaling pathway. J Cell Physiol 234(3):3058–3066
pubmed: 30146703
Dumas EO, Pollack GM (2008) Opioid tolerance development: a pharmacokinetic/pharmacodynamic perspective. AAPS J 10(4):537
pubmed: 18989788
pmcid: 2628209
Trujillo KA (2002) The neurobiology of opiate tolerance, dependence and sensitization: mechanisms of NMDA receptor-dependent synaptic plasticity. Neurotoxicol Res 4(4):373–391
Price DD, Mayer DJ, Mao J, Caruso FS (2000) NMDA-receptor antagonists and opioid receptor interactions as related to analgesia and tolerance. J Pain Symptom Manag 19(1):7–11
Mao J (2002) Role of the glutamatergic system in opioid tolerance and dependence. Glutamate and addiction. Springer, Berlin, pp 281–293
Valdés JJ, Weeks OI (2009) Estradiol and lithium chloride specifically alter NMDA receptor subunit NR1 mRNA and excitotoxicity in primary cultures. Brain Res 1268:1–12
pubmed: 19285052
pmcid: 2681239
Malhi GS, Tanious M, Das P, Coulston CM, Berk M (2013) Potential mechanisms of action of lithium in bipolar disorder. CNS Drugs 27(2):135–153
pubmed: 23371914
Chan P, Lutfy K (2016) Molecular changes in opioid addiction: the role of adenylyl cyclase and cAMP/PKA system. Prog Mol Biol Transl Sci 137:203–227
pubmed: 26810003
Yue X, Varga EV, Stropova D, Vanderah TW, Yamamura HI, Roeske WR (2006) Chronic morphine-mediated adenylyl cyclase superactivation is attenuated by the Raf-1 inhibitor, GW5074. Eur J Pharmacol 540(1–3):57–59
pubmed: 16750187
Belmaker RH, Agam G (2010) The effect of lithium on adenylyl cyclase: thirty-five years of research (1975∼ 2010). Clin Psychopharmacol Neurosci 8:127–132
Mørk A, Geisler A (1989) The effects of lithium in vitro and ex vivo on adenylate cyclase in brain are exerted by distinct mechanisms. Neuropharmacology 28(3):307–311
pubmed: 2542834
Finn AK, Whistler JL (2001) Endocytosis of the mu opioid receptor reduces tolerance and a cellular hallmark of opiate withdrawal. Neuron 32(5):829–839
pubmed: 11738029
Woodgett JR (2001) Judging a protein by more than its name: GSK-3. Sci STKE 2001(100):re12
pubmed: 11579232
Muller DL, Unterwald EM (2004) In vivo regulation of extracellular signal-regulated protein kinase (ERK) and protein kinase B (Akt) phosphorylation by acute and chronic morphine. J Pharmacol Exp Ther 310(2):774–782
pubmed: 15056728
Masvekar RR, El-Hage N, Hauser KF, Knapp PE (2015) GSK3β-activation is a point of convergence for HIV-1 and opiate-mediated interactive neurotoxicity. Mol Cell Neurosci 65:11–20
pubmed: 25616162
pmcid: 4393771