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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2010; 56(6): 39-47


Effect of a new activator of adenosine triphosphate-sensitive potassium channels flocalin on the glucose level in blood

Strutyns'kyĭ RB, Rovenets' RA, Neshcheret OP

    O.O. Bogomoletz Institute of Physiology National Academy of Science of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz56.06.039


Abstract

In experiments on the anaesthetized dogs we investigated the influence of a new fluorine-containing opener of ATP-sensi-tive potassium channels of sarcolemal and mitochondrial membranes flocalin on the level of glucose in arterial blood at physiological conditions and under ischemia (90 min) and reperfusion (180 min) of myocardium. It was shown that in­travenous introduction of flocalin in doses 0,1 - 1,0 mg/kg did not change the level of glucose in blood. In experiments with ischemia-reperfusion of myocardium, flocalin also did not in­crease the level of glucose during all experiment (5,5 hours) after intragastric (with a help of catheter) introduction of drug form (tablets) at cardiorotective dose of 2,2 mg/kg. However, intravenous introduction of flocalin in the dose of 1,5mg/kg, which 15 times exceeded a cardioprotective dose of 0,1mg/kg increased the glucose level 1,33 fold. It should be noted that this increase was not sustained and the level of glucose restored to the initial level within 1 hour. Identical changes of indexes of cardiohemodynamic and the level of glucose in arterial blood under introduction of identical doses of flocalin at the begin­ning and at the end of experiment (total dose of flocalin reached 4 - 4,5 mg/kg) can testify the absence of cumulative effect of flocalin at these experimental conditions. Thus, strong cardioprotective properties, hypotoxicity and the absence of meaningful changes in a carbohydrate exchange allow to consider a new fluorine-containing opener of KATP channels of flocalin as perspective drug for clinical use.

Keywords: KATP-channels, the level of glucose in arterial blood, floñalin, drug form, ischemia-reperfusion

References

  1. Korpachev V.V. kalievie kanali i mehanizmi deistviya proizvodnih sul'fonilmochevini . Ukr. med. chasopis. 2002. N 3. S.16-22.
  2.  
  3. Moibenko O.O., Strutins'kii R.B., Yagupol's'kii L.M., Mohort M.A. Rozrobka ta pidgotovka do vprovadzhennya novogo vitchiznyanogo kardioprotek-tornogo preparatu ftorvmisnogo aktivatora ATF-zalezhnih kaliievih kanaliv Flokalin . Nauka ta innovatsii. 2006. 2, N 4. S.77-82. CrossRef  
  4. Moibenko O.O., Strutins'kii R.B., Yagupol's'kii L.M., Mohort M.A., Shalamai A.S. Organizatsiya zavods'kogo gotovlennya preparatu Flokalin novogo vitchiznyanogo miotropnogo spazmolitika i kardioprotektora . Nauka ta innovatsii. 2009. 5, N 1. S.80-84. CrossRef  
  5. Moybenko OO, Yuzkov M.Ya., Tumanovskaya LV, Kotsyuruba AV Acute myocardial ischemia reperfusion: the role of nitric oxide . Fiziol zh. . 2004. 50, No. 2. P. 34-42.
  6.  
  7. Pivovar S.M. Endogenni mehanizmi kardioprotektsii: Rol' aktivatsii mitohondrial'nih ATF-chutlivih kaliievih kanaliv: Avtoref. dis. ... kand.biol.nauk. 2006. 20 s.
  8.  
  9. Pivovar SM., Strutinsky RB, Yagupolsky LM, Moybenko OO Investigation of the mechanism of action of new fluorine-containing analogues of diazoxide on vascular tone . Fiziol zh. . 2004. 50, No. 2. P. 27-34.
  10.  
  11. Strutinsky RB Vasodilator Effects of Flock-Lin Fluoride Activator of Adenosine Triphosphate-Sensitive Potassium Channels . Fiziol zh. . 2010. 56. N 4. p. 59-65.
  12.  
  13. Strutinsky RB Cardioprotective effects of the dosage form of fluorine-containing activator of adeno-zintrifosfatchitchivy potassium channels of floccalin . Fiziol zh.  - 2009. 55, N 4. P. 83-90.
  14.  
  15. Strutinsky RB, Kotsyuruba AV, Neshcheret OP, Shish AM, Rovenets RA, Moibenko OO Cardioprotective effects of floccalin in in vivo experiments: effect on blood biochemical parameters under myocardial ischemia-reperfusion . Fiziol zh. . N 6. P.12-19.
  16.  
  17. Strutinsky RB, Moybenko OO Modeling the activity of ATP-dependent potassium channels in the aorta of normotensive and hypertensive animals . Ibid. 2000. 46, N 6. p. 54-60.
  18.  
  19. Strutinsky RB, Moybenko OO, Yagupolsky LM Investigation of vasomotor effects of new fluorine-containing synthetic activators of ATP-dependent potassium channels . Fiziol zh. . 2000. N 4. p. 17-23.
  20.  
  21. Strutins'kii P., Mohort M., Yagupol's'kii L., Moibenko O. Flokalin novii vitchiznyanii kardioprotektor . Visn. farmakologii ta farmatsii. 2010. N 3. S. 44-56.
  22.  
  23. Strutinsky RB, Moybenko OO, Yagupolsky LM, Yuzkiv MY, Kvochina LI, Shish A.M. Investigation of cardioprotective effects of a new fluorine activator of ATP-dependent potassium channels . Fiziol zh.  2001. 47, N 2. p. 16-23.
  24.  
  25. Strutinsky RB, Neshcheret OP, Tumanovskaya LV, Rovenets RA, Moybenko OO Cardioprotective effects of floccalin in in vivo experiments: influence on hemodynamics and myocardial lesions under conditions of its ischemia-reperfusion . Fiziol zh. . 2009. 55, N 5. p. 9-16.
  26.  
  27. Strutinskii R.B., Pivovar SM. ATF-zavisimie kalievie kanali i ih rol' kak tsentral'nogo zvenakardioprotektsii pri ishemii-reperfuzii miokar­da. V kn.: Endogennie mehanizmi kardioprotektsii kak osnova patogeneticheskoi terapii zabolevanii serdtsa . K.: Nauk. dumka. 2008. S.206-252.
  28.  
  29. Strutinsky RB, Pivovar SN, Rovenets RA, Shskun OV, Yagupolsky LM, Moibenko OO Influence of activator of adenosine triphosphate-sensitive potassium channels of floccalin on functioning of isolated heart . Fiziol zh. . 2005. 51, No. 6, p. 18-24.
  30.  
  31. Strutinsky RB, Pivovar SM., Tumanovskaya LV, Moybenko OO Cardioprotective effects of floccalin: the relative role of activation of sarcolemmal and mitochondrial adenosine triphosphate-dependent potassium K channels . Fiziol zh. . 2008. 54, N 6. P. 15-23.
  32.  
  33. Strutins'kii R.B., Frantsuzova SB., Rovenets' R.A., Tumanovs'ka L.V., Moibenko O.O. Flokalin novii vitchiznyanii kardioprotektor. V kn.: V Nats. kongres patofiziologiv Ukraini z mizhnar. uchastyu «Suchasni problemi patofiziologii: vid molekulyarno genetichnih do integrativnih aspektiv» (17-19 veresnya 2008 p.). Zaporizhzhya . Patologiya. 2008. 5,N 3. S22.
  34.  
  35. Klebanov B.M., I.I.Malietina, L.M.Yagupol's'kii, Petko K.I., Shavaran S.S. Pat. 17071A Ukraina, MPK6 A 61 K 31. 03. N-(1,2,2 trimetilpropil)-Nuu-tsiano-Nu-arilguanidini z ftorovmisnimi zamisnikami v aromatichnomu yadri, yaki proyavlyayut' gipotenzivnu ta kardiotonichnu diyu N 95041977; Zayav. 26.04.95; Opubl. 31.10.97. Promislova vlasnist'. 1997. N 5. S 3.1.76.
  36.  
  37. Alekseev A.E., Hodgson D.M., Karger A.B., Park S., Zingman L.V., Terzic F. 2005 ATP-sensitive K+ channel channel. enzyme multimer: Metabolic gating in the heart . J. Mol. and Cell Cardiol. 2005. 38. P.895-905. CrossRef PubMed PubMedCentral
  38.  
  39. Ashcroft F.M., Rorsman P. ATP-sensitive K+ channels: A link between b-cell metabolism and insulin secretion . Biochem. Soc. Trans. 1990. N 18. P.109-111. CrossRef PubMed
  40.  
  41. Benndorf K., Thierfelder S., Doepher B., Gebhardt G., Hirche H. Role of Cardiac K Channels During Anoxia and Ischemia . News PhysioTlP Sci . 1997. 12, N 4. P.78-83. CrossRef  
  42. Campbell J.D., Sansom M.S., Ashcroft F.M. Potas­sium channel regulation . EMBO Rep. 2003. 4, N 11. P. 1038-1042. CrossRef PubMed PubMedCentral
  43.  
  44. Dunne M.J., Aynsley-Green A., Lindley K.J. Nature's KATP channels knockout . News Physiol. Sci. 1997. 12. H.197-203. CrossRef  
  45. Flagg T.P., Nichols C.G. Sarcolemmal K channels: what do we really know? . J. Mol. and CeAlTlP Cardiol. 2005. 39. P.61-70. CrossRef PubMed
  46.  
  47. Holmuhamedov E.L., Jovanovic S., Dzeja P.P., Jovanovic A., Terzic A. Mitochondrial ATP-sensitive K+ channels modulate cardiac mitochondrial function . Amer. J. Physiol. Heart Circ. Physiol. 1998. 275. P. 1567-1576. CrossRef PubMed
  48.  
  49. Kawaki J., Nagashima K., Tanaka J., Miki T., Miyazaki M., Ganoi T., Mitsuhashi N., Nakajima N., Iwanaga T., Yano H., Seino S. Unresponsiveness to glibencla-mide during chronic treatment induced by reduction of ATP-sensitive K+ channels activity . Diabetes. 1999. 48. P.2001-2006. CrossRef PubMed
  50.  
  51. Moreau C, Prost A-L., Derand R., Vivaudou M. SUR, ABC proteins targeted by KAT P channels openers . J. Mol. and Cell Cardiol. 2005. 38. P.951-963. CrossRef PubMed
  52.  
  53. Murata M., Akao M., O'Rourke B., Marbbn E. Mito­chondrial ATP-Sensitive potassium channels attenuate matrix Ca2+ overload during simulated ischemia and reperfusion: Possible mechanism of cardioprotection . Circulat. Res. 2001. 89. P. 891-898. CrossRef PubMed
  54.  
  55. Noma A. ATP-regulated K+ channels in cardiac muscle . Nature. 1983. 305. P.147-148. CrossRef PubMed
  56.  
  57. Quayle J.M., Nelson M.T., Standen N.B. ATP-sensitive and inwardly rectifying potassium channels in smooth muscle . Physiol. Rev . 1997. 77, N 4. P.1165-1232. CrossRef PubMed
  58.  
  59. Trapp S., and F.M. Ashcroft. A metabolic sensor in action: news from the ATP-sensitive K+ channel . News Physiol. Sci . 1997. N 12. P.255-263. CrossRef  
  60. Yokoshiki H., Sunagawa M., Seki T., Sperelakis N. ATP-sensitive K+ channels in pancreatic, cardiac, and vascular smooth muscle cells . Amer. J. Physiol. Cell. Physiol. 1998. 274. P. 25-37. CrossRef PubMed
  61.  
  62. Zhang D.X., Chen Y.-F., Campbell W.B., Zou A.-P., Gross G.J., Li P.-L. Characteristics and superoxide induced activation of reconstituted myocardial mito­chondrial ATP-sensitive potassium channels . Circulat. Res. 2001. 89(12). P. 1177-1183. CrossRef PubMed

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