THIOPENTAL BLOCKS K*ATP CHANNELS IN PANCREATIC B-CELL
Keywords:
B-cell, 86Rb, efflux, thiopental, islets of LangerhansAbstract
Objective
To study the effect of thiopental on the permeability to K* of isolated Langerhans islets of rats.
Methods
The islets were isolated by collagenase method and marked for 90 minutes with 86RbCI (K*substitute), then perfused in Krebs-bicarbonate solution in different experimental conditions
Results
The results indicate that the thiopental (0,2 and 2.OmM) reduced the 86Rb efflux of perfused islets, either in glucose presence or in its absence. in solution containing still 20 or 1001lg/ml of tolbutamide, which is a blocker of channels K'
modulated by ATP The inhibiting effect of tiopental in the 86Rb efflux was even more outstanding when the islets perfusion was processed in solution containing diazoxide, substance that opens the K* channels modulated by ATP.
Conclusion
Based on results obtained in experiments with sulphonylureas. it was verified that thiopental acts by blocking preferentially. in a dose-dependent and reversible way, the K' channels modulated by ATP.
Downloads
References
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.
