Inhibition of the NMDA Currents by Probenecid in Amygdaloid Kindling Epilepsy Model.
ATP-binding cassette transporters
Epilepsy
NMDA currents
NMDA receptor
Probenecid
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
30 Jan 2024
30 Jan 2024
Historique:
received:
24
05
2023
accepted:
17
01
2024
medline:
30
1
2024
pubmed:
30
1
2024
entrez:
30
1
2024
Statut:
aheadofprint
Résumé
Epilepsy is characterized by a sustained depolarization and repeated discharge of neurons, attributed to overstimulation of N-methyl-D-aspartate receptors (NMDAr). Herein, we propose that probenecid (PROB), an inhibitor of the activity of some ATP binding-cassette transporters (ABC-transporters) can modify NMDAr activity and expression in amygdaloid kindled model. Some studies have suggested that NMDAr expression could be regulated by inhibiting the activity of P-glycoprotein (MDR1) and drug resistance protein-1 (MRP1). Besides, PROB was found to interact with other proteins with proven activity in the kindling model, such as TRPV2 channels, OAT1, and Panx1. Administering PROB at two doses (100 and 300 mg/kg/d) for 5 d decreased after-discharge duration and Racine behavioral scores. It also reduced the expression of NR2B and the activity of total NOS and the expression of nNOS with respect to the kindling group. In a second protocol, voltage-clamp measurements of NMDA-evoked currents were performed in CA1 hippocampal cells dissociated from control and kindled rats. PROB produced a dose-dependent reduction in NMDA-evoked currents. In neurons from kindled rats, a residual NMDA-evoked current was registered with respect to control animals, while a reduction in NMDA-evoked currents was observed in the presence of 20 mM PROB. Finally, we evaluated the expression of MRP1 and MDR1 in order to establish a relationship between the reduction of kindling parameters, the inhibition of NMDA-type currents, and the expression of these transporters. Based on our results, we conclude that at the concentrations used, PROB inhibits currents evoked by NMDA in dissociated neurons of control and kindled rats. In the kindling model, at the tested doses, PROB decreases the after-discharge duration and Racine behavioral score in the kindling model. We propose a mechanism that could be dependent on the expression of ABC-type transporters.
Identifiants
pubmed: 38289456
doi: 10.1007/s12035-024-03969-0
pii: 10.1007/s12035-024-03969-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
MacDermott AB, Mayer ML, Westbrook GL, Smith SJ, Barker JL (1986) NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones. Nature 321(6069):519–522
pubmed: 3012362
doi: 10.1038/321519a0
Johnson JW, Ascher P (1987) Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature 325(6104):529–531
pubmed: 2433595
doi: 10.1038/325529a0
Nowak L, Bregestovski P, Ascher P, Herbet A, Prochiantz A (1984) Magnesium gates glutamate-activated channels in mouse central neurones. Nature 307(5950):462–465
pubmed: 6320006
doi: 10.1038/307462a0
Mayer ML, Westbrook GL, Guthrie PB (1984) Voltage-dependent block by Mg
pubmed: 6325946
doi: 10.1038/309261a0
Collingridge GL, Bliss TV (1995) Memories of NMDA receptors and LTP. Trends Neurosci 18(2):54–56
pubmed: 7537406
doi: 10.1016/0166-2236(95)80016-U
Bliss TV, Collingridge GL (2013) Expression of NMDA receptor-dependent LTP in the hippocampus: bridging the divide. Mol Brain 6:5
pubmed: 23339575
pmcid: 3562207
doi: 10.1186/1756-6606-6-5
Mody I, Heinemann U (1987) NMDA receptors of dentate gyrus granule cells participate in synaptic transmission following kindling. Nature 326(6114):701–4
pubmed: 3031511
doi: 10.1038/326701a0
Sprengel R, Suchanek B, Amico C et al (1998) Importance of the intracellular domain of NR2 subunits for NMDA receptor function in vivo. Cell 92(2):279–289
pubmed: 9458051
doi: 10.1016/S0092-8674(00)80921-6
Bankstahl JP, Hoffmann K, Bethmann K, Loscher W (2008) Glutamate is critically involved in seizure-induced overexpression of P-glycoprotein in the brain. Neuropharmacology 54(6):1006–1016
pubmed: 18394657
doi: 10.1016/j.neuropharm.2008.02.008
Avemary J, Salvamoser JD, Peraud A et al (2013) Dynamic regulation of P-glycoprotein in human brain capillaries. Mol Pharm 10(9):3333–3341
pubmed: 23924183
doi: 10.1021/mp4001102
Tishler DM, Weinberg KI, Hinton DR, Barbaro N, Annett GM, Raffel C (1995) MDR1 gene expression in brain of patients with medically intractable epilepsy. Epilepsia 36(1):1–6
pubmed: 8001500
doi: 10.1111/j.1528-1157.1995.tb01657.x
Smolarz B, Makowska M, Romanowicz H (2021) Pharmacogenetics of Drug-Resistant Epilepsy (Review of Literature). Int J Mol Sci 22(21):11696
pubmed: 34769124
pmcid: 8584095
doi: 10.3390/ijms222111696
Lazarowski A, Sevlever G, Taratuto A, Massaro M, Rabinowicz A (1999) Tuberous sclerosis associated with MDR1 gene expression and drug-resistant epilepsy. Pediatr Neurol 21(4):731–734
pubmed: 10580886
doi: 10.1016/S0887-8994(99)00074-0
Sisodiya SM, Heffernan J, Squier MV (1999) Over-expression of P-glycoprotein in malformations of cortical development. NeuroReport 10(16):3437–3441
pubmed: 10599858
doi: 10.1097/00001756-199911080-00032
Dombrowski SM, Desai SY, Marroni M et al (2001) Overexpression of multiple drug resistance genes in endothelial cells from patients with refractory epilepsy. Epilepsia 42(12):1501–1506
pubmed: 11879359
doi: 10.1046/j.1528-1157.2001.12301.x
Lazarowski A, Lubieniecki F, Camarero S et al (2004) Multidrug resistance proteins in tuberous sclerosis and refractory epilepsy. Pediatr Neurol 30(2):102–106
pubmed: 14984901
doi: 10.1016/S0887-8994(03)00407-7
Lazarowski A, Massaro M, Schteinschnaider A, Intruvini S, Sevlever G, Rabinowicz A (2004) Neuronal MDR-1 gene expression and persistent low levels of anticonvulsants in a child with refractory epilepsy. Ther Drug Monit 26(1):44–46
pubmed: 14749549
doi: 10.1097/00007691-200402000-00010
Zhu HJ, Liu GQ (2004) Glutamate up-regulates P-glycoprotein expression in rat brain microvessel endothelial cells by an NMDA receptor-mediated mechanism. Life Sci 75(11):1313–1322
pubmed: 15234189
doi: 10.1016/j.lfs.2004.02.027
Yang T, Kong B, Kuang Y et al (2015) Emodin plays an interventional role in epileptic rats via multidrug resistance gene 1 (MDR1). Int J Clin Exp Pathol 8(3):3418–3425
pubmed: 26045880
pmcid: 4440189
Cheng MH, Kim SJ (2020) Inhibitory Effect of Probenecid on Osteoclast Formation via JNK, ROS and COX-2. Biomol Ther (Seoul) 28(1):104–109
pubmed: 31474032
doi: 10.4062/biomolther.2019.047
Du L, Empey PE, Ji J et al (2016) Probenecid and N-Acetylcysteine Prevent Loss of Intracellular Glutathione and Inhibit Neuronal Death after Mechanical Stretch Injury In Vitro. J Neurotrauma 33(20):1913–1917
pubmed: 26830358
pmcid: 5079409
doi: 10.1089/neu.2015.4342
Jiang B, Zhao Y, Cao J et al (2021) Synthesis and preliminary biological evaluation of naproxen-probenecid conjugate for central nervous system (CNS) delivery. Pak J Pharm Sci 34(6):2197–2203
pubmed: 35034881
Vamos E, Voros K, Zadori D, Vecsei L, Klivenyi P (2009) Neuroprotective effects of probenecid in a transgenic animal model of Huntington’s disease. J Neural Transm (Vienna) 116(9):1079–1086
pubmed: 19551467
doi: 10.1007/s00702-009-0253-6
Bang S, Kim KY, Yoo S, Lee SH, Hwang SW (2007) Transient receptor potential V2 expressed in sensory neurons is activated by probenecid. Neurosci Lett 425:120–125
pubmed: 17850966
doi: 10.1016/j.neulet.2007.08.035
SilvermanW LS, Dahl G (2008) Probenecid, a gout remedy, inhibits pannexin 1 channels. Am J Physiol Cell Physiol 295:C761–C767
doi: 10.1152/ajpcell.00227.2008
Taylor DL, Urenjak J, Zilkha E, Obrenovitch TP (1997) Effects of probenecid on the elicitation of spreading depression in the rat striatum. Brain Res 764(1–2):117–125
pubmed: 9295200
doi: 10.1016/S0006-8993(97)00434-4
Urenjak J, Obrenovitch TP, Zilkha E (1997) Effect of probenecid on depolarizations evoked by N-methyl-D-aspartate (NMDA) in the rat striatum. Naunyn Schmiedebergs Arch Pharmacol 355(1):36–42
pubmed: 9007840
doi: 10.1007/PL00004915
Paxinos G, Watson CH (2013) The Rat Brain in Stereotaxic Coordinates, 7th edn. Academic Press, New York
Hernandez-Ceron M, Martinez-Lazcano JC, Rubio C et al (2017) Participation of the dentate-rubral pathway in the kindling model of epilepsy. J Neurosci Res 95(7):1495–1502
pubmed: 27753128
doi: 10.1002/jnr.23974
Goddard GV, McIntyre DC, Leech CK (1969) A permanent change in brain function resulting from daily electrical stimulation. Exp Neurol 25(3):295–330
pubmed: 4981856
doi: 10.1016/0014-4886(69)90128-9
Racine RJ (1972) Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol 32(3):281–94
pubmed: 4110397
doi: 10.1016/0013-4694(72)90177-0
Martinez-Lazcano JC, Gonzalez-Guevara E, Custodio V et al (2018) Activity of nitric oxide synthase isoforms in acute brain oxidative damage induced by ozone exposure. Nitric Oxide 75:42–52
pubmed: 29454052
doi: 10.1016/j.niox.2018.02.004
Martinez-Lazcano JC, Perez-Severiano F, Escalante B et al (2007) Selective protection against oxidative damage in brain of mice with a targeted disruption of the neuronal nitric oxide synthase gene. J Neurosci Res 85(7):1391–1402
pubmed: 17387708
doi: 10.1002/jnr.21261
Bargas J, Howe A, Eberwine J, Cao Y, Surmeier DJ (1994) Cellular and molecular characterization of Ca
pubmed: 7965068
pmcid: 6577263
doi: 10.1523/JNEUROSCI.14-11-06667.1994
Flores-Hernandez J, Galarraga E, Pineda JC, Bargas J (1994) Patterns of excitatory and inhibitory synaptic transmission in the rat neostriatum as revealed by 4-AP. J Neurophysiol 72(5):2246–2256
pubmed: 7884457
doi: 10.1152/jn.1994.72.5.2246
Rendon-Ochoa EA, Hernandez-Flores T, Aviles-Rosas VH et al (2018) Calcium currents in striatal fast-spiking interneurons: dopaminergic modulation of CaV1 channels. BMC Neurosci 19(1):42
pubmed: 30012109
pmcid: 6048700
doi: 10.1186/s12868-018-0441-0
Flores-Hernandez J, Cepeda C, Hernandez-Echeagaray E et al (2002) Dopamine enhancement of NMDA currents in dissociated medium-sized striatal neurons: role of D1 receptors and DARPP-32. J Neurophysiol 88(6):3010–3020
pubmed: 12466426
doi: 10.1152/jn.00361.2002
Campos-Arroyo D, Maldonado V, Bahena I et al (2016) Probenecid Sensitizes Neuroblastoma Cancer Stem Cells to Cisplatin. Cancer Invest 34(3):155–66
pubmed: 26963048
doi: 10.3109/07357907.2016.1139717
Leino E, MacDonald E, Airaksinen MM, Riekkinen PJ (1980) Homovanillic acid and 5-hydroxyindoleacetic acid levels in cerebrospinal fluid of patients with progressive myoclonus epilepsy. Acta Neurol Scand 62(1):41–54
pubmed: 6163302
doi: 10.1111/j.1600-0404.1980.tb03002.x
Shaywitz BA, Cohen DJ, Leckman JF, Young JG, Bowers MB (1980) Ontogeny of dopamine and serotonin metabolites in the cerebrospinal fluid of children with neurological disorders. Dev Med Child Neurol 22(6):748–754
pubmed: 6161049
doi: 10.1111/j.1469-8749.1980.tb03741.x
Fukuyama Y, Ochiai Y (1982) Therapeutic trial by taurine for intractable childhood epilepsies. Brain Dev 4(1):63–69
pubmed: 7039391
doi: 10.1016/S0387-7604(82)80103-4
Tang CM, Dichter M, Morad M (1990) Modulation of the N-methyl-D-aspartate channel by extracellular H+. Proc Natl Acad Sci U S A 87(16):6445–6449
pubmed: 1696732
pmcid: 54551
doi: 10.1073/pnas.87.16.6445
Lipton SA, Rosenberg PA (1994) Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med 330(9):613–622
pubmed: 7905600
doi: 10.1056/NEJM199403033300907
West AE, Chen WG et al (2001) Calcium regulation of neuronal gene expression. Proc Natl Acad Sci U S A 98(20):11024–11031
pubmed: 11572963
pmcid: 58677
doi: 10.1073/pnas.191352298
Banach M, Piskorska B, Czuczwar SJ, Borowicz KK (2011) Nitric oxide, epileptic seizures, and action of antiepileptic drugs. CNS Neurol Disord Drug Targets 10(7):808–819
pubmed: 21999730
doi: 10.2174/187152711798072347
Bankstahl JP, Kuntner C, Abrahim A et al (2008) Langer, Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-11C-verapamil and PET. J Nucl Med 49(8):1328–1335
pubmed: 18632828
doi: 10.2967/jnumed.108.051235
Sutula TP (2004) Mechanisms of epilepsy progression: current theories and perspectives from neuroplasticity in adulthood and development. Epilepsy Res 60(2–3):161–171
pubmed: 15380560
doi: 10.1016/j.eplepsyres.2004.07.001
Sutula TP, Dudek FE (2007) Unmasking recurrent excitation generated by mossy fiber sprouting in the epileptic dentate gyrus: an emergent property of a complex system. Prog Brain Res 163:541–563
pubmed: 17765737
doi: 10.1016/S0079-6123(07)63029-5
McNamara JO (1995) Analyses of the molecular basis of kindling development. Psychiatry Clin Neurosci 49(3):S175–S178
pubmed: 8612137
doi: 10.1111/j.1440-1819.1995.tb02167.x
Kohr G, De Koninck Y, Mody I (1993) Properties of NMDA receptor channels in neurons acutely isolated from epileptic (kindled) rats. J Neurosci 13(8):3612–3627
pubmed: 7688041
pmcid: 6576521
doi: 10.1523/JNEUROSCI.13-08-03612.1993
Behr J, Heinemann U, Mody I (2000) Glutamate receptor activation in the kindled dentate gyrus. Epilepsia 41(Suppl 6):S100–S103
pubmed: 10999529
Kamphuis W, Monyer H, De Rijk TC, Lopes da Silva FH (1992) Hippocampal kindling increases the expression of glutamate receptor-A Flip and -B Flip mRNA in dentate granule cells. Neurosci Lett 148(1–2):51–54
pubmed: 1300503
doi: 10.1016/0304-3940(92)90802-E
Chen YH, Wang CC, Xiao X, Wei L, Xu G (2013) Multidrug resistance-associated protein 1 decreases the concentrations of antiepileptic drugs in cortical extracellular fluid in amygdale kindling rats. Acta Pharmacol Sin 34(4):473–479
pubmed: 23474709
pmcid: 4002787
doi: 10.1038/aps.2012.183
Bauer B, Hartz AM, Pekcec A, Toellner K, Miller DS, Potschka H (2008) Seizure-induced up-regulation of P-glycoprotein at the blood-brain barrier through glutamate and cyclooxygenase-2 signaling. Mol Pharmacol 73(5):1444–1453
pubmed: 18094072
doi: 10.1124/mol.107.041210
García-Rodríguez C, Mujica P, Illanes-González J, López A, Vargas C et al (2023) Probenecid, an Old Drug with Potential New Uses for Central Nervous System Disorders and Neuroinflammation. Biomedicines 11(6):1516
pubmed: 37371611
pmcid: 10295187
doi: 10.3390/biomedicines11061516