Tiopental bloqueia os canais de K+apt nas células B pancreáticas
Palabras clave:
célula B, efluxo de 86Rb, tiopental, ilhotas de LangerhansResumen
Objetivo
Este trabalho estuda o efeito do tiopental sobre a permeabilidade ao K* em ilhotas de Langerhans, isoladas de ratos
Métodos
As ilhotas foram isoladas pelo método da colagenase, marcadas durante 90 minutos com 8'RbCI (substituto de K*) e perfundidas em solução de Krebsbicarbonato em diferentes condições experimentais.
Resultados
Os resultados indicam que o tiopental (0,2 e 2,OmM) reduziu o efluxo de 86Rb de ilhotas perfundidas, tanto na presença quanto na ausência de gIIcose, em solução contendo ainda 20 ou 100Kg/ml de tolbutamida. que é um bloqueador dos canais de K* modulados pelo ATP. O efeito inibidor de tÊopental no efluxo do 86Rb foi mais notável quando a perfusão das ilhotas foi processada em solução contendo diazoxida, substância que abre os canais de K* modulados pelo ATP.
Conclusão
Com base em resultados obtidos em experimentos com sulfoniluréias, constatou-se que o tiopental atua bloqueando preferencialmente, de maneira dose-dependente e reversível, os canaÉs de K* modulados pelo ATP.
Descargas
Citas
Boschero AC. Kawazu S. Duncan G. Malaisse WJ . Effet of glucose on K+ handling by pancreatic islets. Febs Lett. 1977; 83:151-4
Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ. Improved patch-clamp techiniques for high resolution current recordings from cells and cell free membrane patches' Pflugers Arch. 1981 ; 391 (2):85-100
Aguilar BL, Clemente JP, Gonzalez G, Unjlwar K, Babenko A, Bryan J. Toward understanding the assembly and structure of K,„, channel. Physiol Rev. 1998; 78(1):227-45
Seino S. ATP sensitive potassium channels. Annu Rev Physiol. 1999; 61 :337-62
Petersen OH, Maruyama Y. Calcium-activated potassium channels and their role in secretion. Nature (Lond). 1984; 307(5953):693-6
Ashcroft FM. Adenosine 5 -triphosphate sensitive potassium channels. Annu Rev Neurosci. 1988 1 1 :97-135
Petersen OH. Findlay l. Electrophysiology of the pancreas. Physiol Rev. 1987; 67(3):1054-1 16
Rinzel J. Lee YS. Dissection of a model for neuronal parabolic bursting. J Math Biol. 1987; 25(6):653-75.
Malaisse WJ. Meglitinide analogs: new insulinotropic agents for the treatment of non-insulin dependent diabetes. Rev Med Brux. 2003; 24(3):162-8.
ATP-dependerit K* channels. 2000, 176:187-206.
Ashcroft SJH Membrane Biol J
Zünkler BJ, Wos-Maganga M, Panten U. Fluorescence microscopy studies with a fluorescent glibendamide derivative, a high-affinity blocker of pancreatic-cell ATP-sensitive K'currents. Biochern Pharmacol. 2004; 67(8): 1437-44.
Nenquin M, Szoloosi A, Aguilar-Bryan L. Bryan J, Henquin JC. Both triggering and amplifying pathways contribute to fuel-induced insulin secretion in the absence of sulfonylurea receptor-1 in pancreatic beta-cells. J Biol Chem. 2004; 279(31):32316-24.
Hastedt K. Panten U. Inhibition of ATP-sensitive K(+)- channels by a sulfonylurea analogue with a phosphate group. Biochem Pharmacol. 2003; 64(4):599-602.
Sturgess NC, Kozlowski HZ, Carrington CA, Hales CN, Ashford MLJ. Effects of sulphonilureas and diazoxide on insulin secretion and nucleotide sensitive channels in an insulin-secreting cell line. Br J Pharrnacol. 1988; 95(1 ):83-94.
Ashford ML, Sturgess NC, Cook DL, Hales C. K* channels in an insulin-secreting cell line: effects of ATP and sulphonylureas. In: Atwater 1, Rojas E, Sonia B, editors. Biophysics of the pancreatic B-cell. New York: Plenum Press; 1986. p.69-76.
Ashcroft FM, Rorsman, P. Electrophysiology of the pancreatic-cell. Prog BÊophys Mol Biol. 1991 ; 54(1 ):87-143 .
, Zunkler BJ. Lensen S, Manner K. Panten U, Trube G Concentration dependent effects of tolbutamide, meglitinide, glipizide, glibenclamide. and diazoxide on ATP-regulated K+ currents in pancreatic B-cells. Naunyn- Schmiedebergs. Arch Pharmacol. 1988; 337(2):225-30.
Arkhammar P, Nilsson T, Rorsman P, Berggren PO. Inhibition of ATP regulated K channels precedes despolarization induced increase in cytoplasmic free Ca2* concentratÊon in pancreatic P-cells. J Biol Chem 1987; 262(12):5448-54
Schwartz JR. The mode of action of phenobarbital on the excitabie membrane of the node of ranvier. Eur J Pharmacol. 1979; 56:51-60
Sevcik C. Differences between the action of thÊopental and pentobarbital in squid giant axon. J Pharmacol Exp Ther. 1980; 214(3):657-63
. Boschero AC. Delattre E, Dos Santos ML. Isolamento de ilhotas de Langerhans de rato, Resumos do 22'’ Congresso de SBFis; 1980; Ribeirão Preto, SP p.117
Boschero AC, Malaisse WJ. StÊmulus-secretion coupling of glucose induced insulin release. XXIX regulation of 86Rb efflux from perfused Êslets. Am J Physiol, 1979; 236(2):E139-46
Ho IK, Harris RA, Mechanism of action of barbiturates. Ann Rev Pharmacol Toxtcol. 1981; 21 :83-111.
Silva CA. Permeability to K* in pancreatic B cell [dissertação]. Campinas: Instituto de Biologia, Universidade Estadual de Campinas; 1997. 98p.
Malaisse WJ. Boschero AC, Kawazu S, Hutton IC. The stimulus-secretion coupling of glucose-induced- -insulin release. Effect of glucose on K+ fluxes in Êsolated islets. Pflugers Arch. 1978; 373:237-242
Henquin JC, Meissner HP. Opposite effects of tolbutamide and diazoxide on 86Rb fluxes and membrane potential in pancreatic í3 ceIÉs. Biochern Pharmacol. 1982; 31(7):1407-1 5
Rossmann P, Trube G. Glucose dependent K' channels in pancreatic beta cells are reguÉated by intracelular ATP. Pflugers Arch. 1985; 405:305-9
Gonçalves AA, Silva CA. Potassium permeability in pancreatic B-cell. The effect of thiopental. Brazilian J Med Biol Res, 1988; 21 (2):365-8
Kozlowski RZ. Hales CN. Noble AL, Ashford MLJ. The ATP-K+ channel; a novel site of action for the barbiturates, Diabetologia. 1989; 32:506A.