Ex-vivo modulation of spontaneous uterine contractility by some sodium ion channel blockers
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Local anaesthetics of the amide class which act by sodium ion (Na+) channel blockade had been reported to stimulate uterine contractility rather than cause inhibition. This study therefore sets out to investigate the effect of selected Na+ channel blockers that do not belong to the class of local anaesthetics, on uterine contractility. This was necessary in order to ascertain if the effect previously observed with the amide anaesthetics were a function of the class of anaesthetics, a function of Na+ channel blockade or other interactions. Three Na+ channel blocking drugs and one amide anaesthetic drug were used for the investigation. These included: lidocaine (0.0002 - 2.222 ?g/ml), quinine (0.003 - 1.332 ?g/ml), chloroquine (0.64 -710 ng/ml) and phenytoin (0.001 - 1.11 ?g/ml). These drugs were added cumulatively to the isolated mouse uterus which was mounted in a 10 ml organ bath filled with continuously aerated physiological solution and set at a temperature of 37ºC. The effect of these drugs on the amplitude and frequency of spontaneous uterine contractions were determined. Lidocaine, quinine and chloroquine were observed to concentration-dependently increase the amplitude and frequency of uterine spontaneous contractions (p < 0.05). However, phenytoin was observed to decrease both the amplitude and frequency of uterine spontaneous contractions (p < 0.05). The stimulation contradicts the effect of Na+-channel blockade on smooth muscle contractility and therefore suggests other mechanism(s) of activity apart from Na+-channel blockade or a new role for Na+-channel blockade on uterine smooth muscles. This study has shown that besides the amide anaesthetics, other Na+-channel blocking drugs produce stimulation of uterine contractility.
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Références
Antzelevitch, C., Brugada, P., Brugada, J., Brugada, R., Towbin, J.A., Nademanee, K., (2003). Brugada syndrome: 1992-2002: A historical perspective. J. Am. Coll. Cardiol. 41:1665–1671. doi:10.1016/S0735-1097(03)00310-3
Ashcroft, F.M., (2006). From molecule to malady. Nature 440:440–447. doi:10.1038/nature04707
Bafor, E.E., Obarisiagbon, P.A., Itamaomon, J.L., (2015). Investigation of The Myometrial Stimulatory Effect of Amide Anaesthetics. J. Pharm. Allied Sci. 12: 2191–2209.
Catterall, W.A., (2012). Voltage-gated sodium channels at 60: structure, function and pathophysiology. J. Physiol. 590: 2577–2589. doi:10.1113/jphysiol.2011.224204
Chanrachakul, B., (2006). Ion channels: new targets for the next generation of tocolytics agents. J. Med. Assoc. Thai. 89: Suppl 4.
Clare, J.J., Tate, S.N., Nobbs, M., Romanos, M.A., (2000). Voltage-gated sodium channels as therapeutic targets. Drug Discov.Today. 5(11):506-520. doi:10.1016/S1359-6446(00)01570-1
Goldin, A.L., (2001). Resurgence of sodium channel research. Annu. Rev. Physiol. 63:871–894. doi:10.1146/annurev.physiol.63.1.871r63/1/871 [pii]
Hille, B., (2001). Ionic channels of excitable membranes, 3rd ed. Sinauer Associates Inc., MA, Sunderland.
Hille, B., (1977). Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction. J. Gen. Physiol. 69: 497–515. doi:10.1085/jgp.69.4.497
Inoue, Y., Sperelakis, N., (1991). Gestational change in Na+ and Ca2+ channel current densities in rat myometrial smooth muscle cells. Am J Physiol 260: C658-663.
Lipkind, G.M., Fozzard, H.A., (2010). Molecular model of anticonvulsant drug binding to the voltage-gated sodium channel inner pore. Mol. Pharmacol. 78: 631–638. doi:10.1124/mol.110.064683
Martin, C., Arnaudeau, S., Jmari, K., Rakotoarisoa, L., Sayet, I., Dacquet, C., Mironneau, C., Mironneau, J., (1990). Identification and properties of voltage-sensitive sodium channels in smooth muscle cells from pregnant rat myometrium. Mol. Pharmacol. 38: 667–673.
Martin, L.J., Corry, B., (2014). Locating the Route of Entry and Binding Sites of Benzocaine and Phenytoin in a Bacterial Voltage Gated Sodium Channel. PLoS Comput. Biol. 10 (7):e1003688. doi:10.1371/journal.pcbi.1003688
Nardi, A., Damann, N., Hertrampf, T., Kless, A., (2012). Advances in Targeting Voltage-Gated Sodium Channels with Small Molecules. Chem. Med. Chem. 7(10):1712-1740. doi:10.1002/cmdc.201200298
Seda, M., Pinto, F.M., Wray, S., Cintado, C.G., Noheda, P., Buschmann, H., Candenas, L., (2007). Functional and molecular characterization of voltage-gated sodium channels in uteri from nonpregnant rats. Biol. Reprod. 77: 855–863. doi:10.1095/biolreprod.107.063016
Sperelakis, N., Inoue, Y., Ohya, Y., (1992). Fast Na+ channels and slow Ca2+ current in smooth muscle from pregnant rat uterus. Mol. Cell. Biochem. 114: 79–89. doi:10.1007/BF00240301
Waxman, S.G., (2007). Channel, neuronal and clinical function in sodium channelopathies: from genotype to phenotype. Nat. Neurosci. 10: 405–409. doi:10.1038/nn1857
Yoshino, M., Wang, S.Y., Kao, C.Y., (1997). Sodium and calcium inward currents in freshly dissociated smooth myocytes of rat uterus. J. Gen. Physiol. 110: 565–577. doi:10.1085/jgp.110.5.565
Young, R.C., Herndon-Smith, L., (1991). Characterization of sodium channels in cultured human uterine smooth muscle cells. Am. J. Obstet. Gynecol. 164: 175–181.
Yu, F.H., Catterall, W.A., (2003). Overview of the voltage-gated sodium channel family. Genome Biol. 4(3): 207. doi:10.1186/gb-2003-4-3-207
Zuliani, V., Patel, M.K., Fantini, M., Rivara, M., (2009). Recent advances in the medicinal chemistry of sodium channel blockers and their therapeutic potential. Curr. Top. Med. Chem. 9: 396–415.