Cholecystokinin octapeptide increases free intracellular calcium of guinea pig cardiomyocytes through activation of Ca2+ channel and tyrosine kinase

( views:66, downloads:0 )
Journal Title:
Volume 56, Issue 01, 2004
Key Word:
cholecystokinin;cardiomyocyte;fluorescent intensity;Ca2+ channel;confocal microscopy;receptor

Abstract: The aim of the present study was to explore the effect of cholecystokinin octapeptide (CCK-8) on [Ca2+]i and its signal transduction mechanism in isolated guinea pig cardiomyocytes. [Ca2+]i was measured by laser scanning confocal microscopy in single ventricular myocytes which were dissociated by enzymatic dissociation method and loaded with Fluo 3-AM.The changes in [Ca2+]i were represented by fluorescent intensity (Fi) or relative fluorescent intensity (Fi/Fo%). The results obtained are as follows. (1) In the normal Tyrode's solution containing 1.0 mmol/L Ca2+, CCK-8 (1~104pmol/L) elicited a rapid and marked increase in [Ca2+]i (2) When cardiomyocytes were pretreated with the Ca2+ chelator EGTA (3 mmol/L) and Ca2+channel antagonist nisoldipine (0.5 μmol/L) for 5 min, CCK-8 (102 pmol/L) caused a slow and small increase in [Ca2+]i (P<0.01). (3) Pretreatment with the nonselected CCK- receptor (CCK-R) antagonist proglumide (6 μmol/L) or the tyrosine kinase inhibitor genistein (1 μmol/L) for 5 min could inhibit the increase of [Ca2+]i induced by CCK-8 (102 pmol/L) (P<0.01).The results suggest that CCK-8 increases the [Ca2+]i via activating the receptor-operated Ca2+ channel and eliciting the influx of Ca2+ in isolated guinea pig cardiomyocytes, in which tyrosine kinase may be involved.

  • [1]Crawley JN,Corwin RL. Biological actions of cholecystokinin. Peptides 1994; 15(4):731-755.
  • [2]Janssen PJ, Gardiner SM, Compton AM, Bennett T.Mechanisms contributing to the differential haemodynamic effects of bombesin and cholecystokinin in conscious Long Evans rats. Br J Pharmacol 1991;102(1): 123-134.
  • [3]Gaw AG, Hills DM, Spraggs CF. Characterization of the receptors and mechanisms involved in the cardiovasculai actions of sCCK-8 in the pithed rat. Br J Pharmacol 1995;115(4):660-664.
  • [4]Bunting MW, Beart PM, Widdop RE. Effects of the CCK (A) receptor antagonists SR 27897B and PD140548 on haroreflex function in conscious rats Eur J Pharmacol 1997;337(1):35-39.
  • [5]Zhao XY, Ling YL, Meng AH, Shan BE, Zhang JL.Effects of cholecystokinin octapeptide on rat cardiac function and the receptor mechanism. Acta Physiol Sin (生理学报) 2002;54(3):239-243.
  • [6]Rubin LJ, Keller RS, Parker JL, Adams HR. Contractile dysfunction of ventricular myocytes isolated from endotoxemic guinea pigs. Shock 1994;2(2): 113-120.
  • [7]Li BY, Fu B, Zhao YL, Li WH. Effect of berbamine on intracellular calcium concentration in cultured HeLa cells.Acta Pharmacol Sin 1999;51(11):1011-1014.
  • [8]Qiu LY (邱丽颖,), Chen YJ, Ge FG, Wang DB. An analysis of ionic flow of spontaneous slow action potential of guinea pig aortic vestibule. Acta Physiol Sin (生理学报) 2000;52(4):308-312 (Chinese, English abstract).
  • [9]Yule DI, Tseng M J, Williams JA, Logdson CD. A cloned CCK-A receptor transduces multiple signals in response to full and partial agonists. Am J Physiol 1993;265(5):G999-G 1004.
  • [10]Tapia JA, Fen-is HA, Jensen RT, Garcia LJ. Cholecystokinin activates PYK2/CAKβ by a phospholipase C- dependent mechanism and its association with the mitogen-activated protein kinase signaling pathway in pancreatic acinar cells. J Biol Chem 1999;274(44): 31261-31271.
  • [11]Lutz MP, Sutor SL, Abraham RT, Miller LJ. A role for cholecystokinin-stimulated protein tyrosine phosphorylation in regulated secretion by the pancreatic acinar cell. J Biol Chem 1993 ;268(15): 11119-11124.
  • [12]Katsube Y, Yokoshiki H, Nguyen L, Yamamoto M, Sperelakis N. Inhibition of Ca2+ current in neonatal and adult rat ventricular myocytes by the tyrosine kinase inhibitor,genistein. J Eur Pharmacol 1998;345(3):309-314.
  • [13]Taskinen P, Toth M, Ruskoaho H. Effects of genistein on cardiac contractile force and atrial natriuretic peptide secretion in the isolated perfused rat heart. Eur J Pharmacol 1994; 256(3):251-261.
WanfangData CO.,Ltd All Rights Reserved
About WanfangData | Contact US
Healthcare Department, Fuxing Road NO.15, Haidian District Beijing, 100038 P.R.China
Tel:+86-010-58882616 Fax:+86-010-58882615