[en] BACKGROUND: Propofol is a widely used intravenous general anesthetic. Acetylcholine (ACh) is critical in controlling epithelial ion transport. This study was to investigate the effects of propofol on ACh-evoked secretion in rat ileum epithelium.
METHODS: The Ussing chamber technique was used to investigate the effects of propofol on carbachol (CCh)-evoked short-circuit currents (Isc).
KEY RESULTS: Propofol (10-2 -10-6 mol/L) attenuated CCh-evoked Isc of rat ileum mucosa in a dose-dependent manner. The inhibitory effect of propofol was only evident after application to the serosal side. Pretreatment with tetrodotoxin (TTX, 0.3 μmol/L, n=5) had no effect on propofol-induced inhibitory effect, whereas serosal application of K+ channel inhibitor, glibenclamide, but not, an ATP-sensitive K+ channel inhibitor, largely reduced the inhibitory effect of propofol. In addition, pretreatment with either hexamethonium bromide (HB, nicotinic nACh receptor antagonist) or Cl- channel blockers niflumic acid and cystic fibrosis transmembrane conductance regulator (inh)-172 did not produce any effect on the propofol-induced inhibitory effect.
CONCLUSIONS & INFERENCES: Propofol inhibits CCh-induced intestinal secretion by directly targeting basolateral K+ channels.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Tang, S-H; Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan, China
Wang, H-Y; Department of Physiology, School of Medicine, Shandong University, Jinan, China
Sun, H; Department of Thoracic Surgery, Shandong Tumor Hospital, Shandong University, Jinan, China
An, Ning ; Université de Liège - ULiège > GIGA > GIGA Stem Cells - Cancer Signaling ; Department of Physiology, School of Medicine, Shandong University, Jinan, China
Xiao, L; Department of Physiology, School of Medicine, Shandong University, Jinan, China
Sun, Q; Department of Physiology, School of Medicine, Shandong University, Jinan, China
Zhao, D-B; Department of Thoracic Surgery, Shandong Tumor Hospital, Shandong University, Jinan, China
Language :
English
Title :
Propofol inhibits carbachol-induced chloride secretion by directly targeting the basolateral K+ channel in rat ileum epithelium.
This study was granted by the Fundamental Research Funds of Shandong University (2014QLKY08). This work was supported by the Fundamental Research Funds of Shandong University (2014QLKY08).
Hirota CL, McKay DM. Cholinergic regulation of epithelial ion transport in the mammalian intestine. Br J Pharmacol. 2006;149:463–479.
Field M. Intestinal ion transport and the pathophysiology of diarrhea. J Clin Invest. 2003;111:931–943.
Kawashima K, Fujii T. Basic and clinical aspects of non-neuronal acetylcholine: overview of non-neuronal cholinergic systems and their biological significance. J Pharmacol Sci. 2008;106:167–173.
Caulfield MP, Birdsall NJ. International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors. Pharmacol Rev. 1998;50:279–290.
Levey AI. Immunological localization of m1-m5 muscarinic acetylcholine receptors in peripheral tissues and brain. Life Sci. 1993;52:441–448.
Wall SJ, Yasuda RP, Li M, Wolfe BB. Development of an antiserum against m3 muscarinic receptors: distribution of m3 receptors in rat tissues and clonal cell lines. Mol Pharmacol. 1991;40:783–789.
Kachur JF, Sturm BL, Gaginella TS, Noronha-Blob L. Regulation of guinea pig ileal electrolyte transport by M3-muscarinic acetylcholine receptors in vitro. Mol Pharmacol. 1990;38:836–840.
Keely SJ. Epithelial acetylcholine–a new paradigm for cholinergic regulation of intestinal fluid and electrolyte transport. J Physiol. 2011;589:771–772.
Yajima T, Inoue R, Matsumoto M, Yajima M. Non-neuronal release of ACh plays a key role in secretory response to luminal propionate in rat colon. J Physiol. 2011;589:953–962.
Karaki SI, Kuwahara A. Regulation of intestinal secretion involved in the interaction between neurotransmitters and prostaglandin E2. Neurogastroenterol Motil. 2004;16(suppl 1):96–99.
Khan MR, Anisuzzaman AS, Semba S, et al. M1 is a major subtype of muscarinic acetylcholine receptors on mouse colonic epithelial cells. J Gastroenterol. 2013;48:885–896.
Bieda MC, MacIver MB. Major role for tonic GABAA conductances in anesthetic suppression of intrinsic neuronal excitability. J Neurophysiol. 2004;92:1658–1667.
Orser BA, Wang LY, Pennefather PS, MacDonald JF. Propofol modulates activation and desensitization of GABAA receptors in cultured murine hippocampal neurons. J Neurosci. 1994;14:7747–7760.
Nagase Y, Kaibara M, Uezono Y, Izumi F, Sumikawa K, Taniyama K. Propofol inhibits muscarinic acetylcholine receptor-mediated signal transduction in Xenopus Oocytes expressing the rat M1 receptor. Jpn J Pharmacol. 1999;79:319–325.
Wachtel RE, Wegrzynowicz ES. Kinetics of nicotinic acetylcholine ion channels in the presence of intravenous anaesthetics and induction agents. Br J Pharmacol. 1992;106:623–627.
Tang J, Jiang Y, Tang Y, et al. Effects of propofol on damage of rat intestinal epithelial cells induced by heat stress and lipopolysaccharides. Braz J Med Biol Res. 2013;46:507–512.
Li Y, Li XF, Hua G, et al. Colonic submucosal 5-HT(3) receptor-mediated somatostatin-dependent secretoinhibitory pathway is suppressed in water-immersion restraint stressed rats. Eur J Pharmacol. 2011;656:94–100.
Dickinson KE, Frizzell RA, Sekar MC. Activation of T84 cell chloride channels by carbachol involves a phosphoinositide-coupled muscarinic M3 receptor. Eur J Pharmacol. 1992;225:291–298.
Sayer B, Lu J, Green C, Soderholm JD, Akhtar M, McKay DM. Dextran sodium sulphate-induced colitis perturbs muscarinic cholinergic control of colonic epithelial ion transport. Br J Pharmacol. 2002;135:1794–1800.
Murasaki O, Kaibara M, Nagase Y, et al. Site of action of the general anesthetic propofol in muscarinic M1 receptor-mediated signal transduction. J Pharmacol Exp Ther. 2003;307:995–1000.
Cliff WH, Frizzell RA. Separate Cl− conductances activated by cAMP and Ca2+ in Cl(-)-secreting epithelial cells. Proc Natl Acad Sci USA. 1990;87:4956–4960.
Devor DC, Simasko SM, Duffey ME. Carbachol induces oscillations of membrane potassium conductance in a colonic cell line, T84. Am J Physiol. 1990;258:C318–C326.
Venglarik CJ, Bridges RJ, Frizzell RA. A simple assay for agonist-regulated Cl and K conductances in salt-secreting epithelial cells. Am J Physiol. 1990;259:C358–C364.
Barrett KE, Keely SJ. Chloride secretion by the intestinal epithelium: molecular basis and regulatory aspects. Annu Rev Physiol. 2000;62:535–572.
Hardcastle J, Hardcastle PT, Noble JM. The involvement of calcium in the intestinal response to secretagogues in the rat. J Physiol. 1984;355:465–478.
Hardcastle J, Hardcastle PT. The involvement of basolateral potassium channels in the intestinal response to secretagogues in the rat. J Physiol. 1986;379:331–345.
Epple HJ, Fromm M, Riecken EO, Schulzke JD. Antisecretory effect of loperamide in colon epithelial cells by inhibition of basolateral K+ conductance. Scand J Gastroenterol. 2001;36:731–737.
Krantis A. GABA in the mammalian enteric nervous system. News Physiol Sci. 2000;15:284–290.