Background: Active and significant relaxation of the human gallbladder must be one of the facets of its motility during both the filling and emptying cycle. Conflicting reports about the presence or significance of nitric oxide have been reported in the literature. The aim of this study was to investigate the role of nitric oxide and KATP channels in human gallbladder muscle using isolated strips from human gallbladder. Methods: Full thickness strips were obtained from 56 human gallbladders and suspended under isometric tension in organ baths. The effect of nitric oxide donors and inhibitors on cholecystokinin octapeptide- and carbachol-induced contraction was examined. In separate experiments the effect of the KATP channel activator, cromakalim, and the inhibitor, glibenclamide, were determined. Results: Cromakalim induced a significant relaxation of agonist-induced contraction in human gallbladder in vitro, an effect which was abolished by the KATP channel inhibitor glibenclamide. No evidence of significant nitric oxide involvement in relaxation was observed. Conclusions: This study has demonstrated the presence of KATP channels in human gallbladder for the first time. These are capable of causing significant relaxation in the presence of hormonal and muscarinic agonists and may represent a major pathway for gallbladder relaxation.

Lanzini A, Jazrawi RP, Northfield TC: Simultaneous quantitative measurements of absolute gallbladder storage and emptying during fasting and eating in humans. Gastroenterology 1987;92:852–861.
Lanzini A, Northfield TC: Gallbladder Motor Function in Man. Bile Acids in Health and Disease. Amsterdam, Kluwer Academic Publishers 1988, pp 83–96.
Lanzini A, Northfield TC: Assessment of the motor functions of the gallbladder. J Hepatol 1989;9:383–391.
Abiru H, Sarna SK, Condon RE: Contractile mechanisms of gallbladder filling and emptying in dogs. Gastroenterology 1994;106:1652–1661.
Geenen JE, Hogan WJ, Dodds WJ, Stewart ET, Arndorfer RC: Intraluminal pressure recording form the human sphincter of Oddi. Gastroenterology 1980;78:317–324.
Dodds WJ, Hogan WJ, Geenen JE: Motility of the biliary system; in: Wood J (ed): Handbook of Physiology. Section 6: The Gastrointestinal System. Vol 1: Motility and Circulation. Part II. Bethesda, American Physiological Society, 1989.
Thompson JC, Fender HR, Ramus I, Villar HV, Rayford PL: Cholecystokinin metabolism in man and dogs. Ann Surg 1975;182:496–504.
Feeley TM, Clanachan AS, Baer HP, Scott GW: Contractility and sensitivity of normal and diseased human gallbladder and cystic duct to cholecystokinin. Surg Forum 1983;34:236–238.
Severi C, Grider JR, Makhlouf GM: Functional gradients in muscle cells isolated from gallbladder, cystic duct and common bile duct. Am J Physiol 1988;255:G647–G652.
Feeley TM, Clanachan AS, Scott GW: The effects of vasoactive intestinal polypeptide on the motility of human and guinea pig gallbladder. Can J Physiol Pharmacol 1983;621:356–359.
Andersson KE, Hedner P, Persson CGA: Differentiation of the contractile effects of prostaglandins E2 and the C terminal octapeptide of cholecystokinin in isolated guinea pig gallbladder. Acta Physiol Scand 1974;90:657–663.
Nakano J, McCloy RF, Gin AC, Nakano SK: Effect of prostaglandins E1, E2 and F2a and pentagastrin on gallbladder pressure in dogs. Eur J Pharmacol 1975;30:107–112.
Thornell E: Mechanisms in the development of acute cholecystitis and biliary pain. Scand J Gastroenterol 1982;17(suppl 76):1–31.
Furchgott RF, Zawadzki JV: The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980;288:373–376.
Talmage EK, Mawe GM: NADPH-diaphorase and VIP are co-localized in neurons of gallbladder ganglia. J Auton Nerv Syst 1993;43:83–89.
Talmage EK, Pouliot WA, Schemann M, Mawe GM: Structure and chemical coding of human, canine and opossum gallbladder ganglia. Cell Tissue Res 1996;285:289–302.
Mourelle M, Guarner F, Molero X, Moncada S, Malagelada J-R: Regulation of gall bladder motility by the arginine-nitric oxide pathway in guinea pigs. Gut 1993;34:911–915.
Edwards G, Weston H: Potassium channel openers and vascular smooth muscle relaxation. Pharmacol Ther 1990;48:237–258.
Wegstapel H, Bird NC, Chess-Williams R, Johnson AG: The relationship between in vivo emptying of the gallbladder, biliary pain and in vitro contractility of the gallbladder in patients with gallstones: Is biliary colic muscular in origin? Scand J Gastroenterol 1999;34:421–425.
Parker JL, Mattox ML, Laughlin MH: Contractile responsiveness of coronary arteries from exercise-trained rats. J Appl Physiol 1997;83:434–443.
Schmid-Antomarchi H, De Weille J, Fosset M, Lazdunski M: The receptor for antidiabetic sulphonylures controls the activity of the ATP-modulated K+ channel in insulin secreting cells. J Biol Chem 1987;262:15840–15844.
Chen Q, Amaral J, Ho S, Biancani P, Behar J: Gallbladder relaxation in patients with pigment and cholesterol stones. Gastroenterology 1997;113:930–937.
Chen Q, Lee K, Xiao Z, Biancani P, Behar J. Mechanism of gallbladder relaxation in the cat: Role of norepinephrine. J Pharmacol Exp Ther 1998;285:475–479.
McKirdy ML, McKirdy HC, Johnson CD: Non-adrenergic non-cholinergic inhibitory innervation shown by electrical field stimulation of isolated strips of human gall bladder muscle. Gut 1994;35:412–416.
Luman W, Ardill JE, Armstrong E, Smith GD, Brett L, Lessells AM, Haynes WG, Gray GA, Mickley EJ, Webb DJ, Palmer KR: Nitric oxide and gallbladder motor function. Aliment Pharmacol Ther 1998;12:425–432.
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