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Effects of bioactive agents on biliary motor function

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Abstract

Our understanding of biliary motility under normal and pathophysiologic conditions is still incomplete, but there have been recent advances. Of particular interest are the mechanisms involved in gallbladder filling and emptying, with a focus on understanding the processes underlying impaired gallbladder emptying leading to gallbladder dyskinesia and the formation of gallstones or cholecystitis. The sphincter of Oddi (SO) is a complex neuromuscular structure. Recent studies have attempted to unravel the specific neural or hormonal mechanisms operating under normal physiologic conditions and those that may lead to SO dysfunction. Furthermore, new research fronts are emerging, including the role of leptin in obese patients with impaired biliary motility and the action of electroacupuncture for possible treatment of SO dysfunction. This review illustrates the broad front of current research regarding the effects of bioactive agents on biliary motility, including enteric hormones, nitric oxide, opioids, inflammatory mediators, leptin, protease inhibitors, neurotransmitters, and electroacupuncture.

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References and Recommended Reading

  1. Rehfeld JF, Sun G, Christensen T, et al.: The predominant cholecystokinin in human plasma and intestine is cholecystokinin-33. J Clin Endocrinol Metab 2001, 86:251–258.

    Article  PubMed  CAS  Google Scholar 

  2. Hogenauer C, Meyer RL, Netto GJ, et al.: Malabsorption due to cholecystokinin deficiency in a patient with autoimmune polyglandular syndrome type I. N Engl J Med 2001, 344:270–274. This case report describes a patient with severe malabsorption who exhibited a deficiency of CCK-producing enteroendocrine cells in the proximal small intestine. CCK was absent in the serum, and the gallbladder failed to empty to a meal. These findings reaffirm the prominent role of CCK in gallbladder emptying.

    Article  PubMed  CAS  Google Scholar 

  3. Vu MK, van Oostayen JA, Biemond I, et al.: Effect of somatostatin on postprandial gallbladder relaxation. Clin Physiol 2001, 21:25–31. Although this human study suggests that somatostatin has the physiologic role of relaxing the gallbladder to enhance refilling in the late prandial phase, the authors do not offer any evidence that release of this paracrine hormone predominates in this period.

    Article  PubMed  CAS  Google Scholar 

  4. Maselli MA, Piepoli AL, Pezzolla F, et al.: Effect of somatostatin on human gallbladder motility: an in vitro study. Neurogastroenterol Motil 1999, 11:47–53.

    Article  PubMed  CAS  Google Scholar 

  5. Hoentjen F, Hopman WPM, Jansen JBMJ: Effect of circulating peptide YY on gallbladder emptying in humans. Scand J Gastroenterol 2001, 36:1086–1091.

    Article  PubMed  CAS  Google Scholar 

  6. Meedeniya ACB, Al-Jiffry BO, Konomi H, et al.: Inhibitory motor innervation of the gall bladder musculature by intrinsic neurones containing nitric oxide in the Australian Brush-tailed possum (Trichosurus vulpecula). Gut 2001, 49:692–698.

    Article  PubMed  CAS  Google Scholar 

  7. Mawe GM, Ellis LM: Chemical coding of intrinsic and extrinsic nerves in the guinea pig gallbladder: Distributions of PACAP and orphanin FQ. Anat Rec 2001, 262:101–109.

    Article  PubMed  CAS  Google Scholar 

  8. Greaves RRSH, O’Donnell LJD, Battistini B, et al.: The differential effect of VIP and PACAP on guinea pig gallbladder in vitro. Eur J Gastroenterol Hepatol 2000, 12:1181–1184.

    Article  PubMed  CAS  Google Scholar 

  9. Alcon S, Morales S, Camello PJ, et al.: Relaxation of the canine gallbladder to nerve stimulation involves adrenergic and non-adrenergic non-cholinergic mechanisms. Neurogastro Motil 2001, 13:555–566.

    Article  CAS  Google Scholar 

  10. Alcon S, Morales S, Camello PJ, et al.: A redox-based mechanism for the contractile and relaxing effects of NO in the guinea-pig gall bladder. J Physiol (London) 2001, 532:793–810.

    Article  CAS  Google Scholar 

  11. Guarraci FA, Pozo MJ, Palomares SM, et al.: Opioid agonists inhibit excitatory neurotransmission in ganglia and at the neuromuscular junction in guinea pig gallbladder. Gastroenterology 2002, 122:340–351. This paper demonstrates that all three types of opiate receptors are located on nerve terminals in the gallbladder wall and that opioid agonists can potently inhibit excitatory neural input to gallbladder neurons and smooth muscle. This mechanism is likely to contribute to acalculous cholecystitis, which is common in individuals who suffer from severe pain following trauma or extensive surgical procedures, and who often receive opiate analgesics.

    Article  PubMed  CAS  Google Scholar 

  12. Al-Jiffry BO, Meedeniya ACB, Chen JW, et al.: Endothelin-1 induces contraction of human and Australian possum gallbladder in vitro. Regul Pept 2001, 102:31–39.

    Article  PubMed  CAS  Google Scholar 

  13. Al-Jiffry BO, Toouli J, Saccone GTP: Endothelin-3 induces both human and possum gallbladder contraction mediated mainly by endothelin-B receptor subtype in vitro. J Gastroenterol Hepatol 2002, 17:324–331.

    Article  PubMed  CAS  Google Scholar 

  14. Huang SC, Lee MC, Wei CK, et al.: Endothelin receptors in human and guinea-pig gallbladder muscle. Regul Pept 2001, 98:145–153. This study compared the characteristics of the actions of endothelin on human and guinea pig gallbladder. Using organ bath pharmacology, binding studies, and autoradiography, this study showed that ET-1, ET-2, and ET-3 cause smooth muscle contraction by binding to ETA and ETB receptors located on the smooth muscle, with cooperation between receptors. The findings were similar with human and guinea pig tissues.

    Article  PubMed  CAS  Google Scholar 

  15. Cardozo AM, Koepp J, D’ Orleans-Juste P, et al.: Receptors mediating endothelin-1-induced contractions of rabbit gallbladder. J Cardiovasc Pharmacol 2000, 36:S264-S266.

    PubMed  CAS  Google Scholar 

  16. Nora HC, Cardozo AM, D’Orleans-Juste P, et al.: Influences of indomethacin on contractions induced by endothelins in guinea pig isolated gallbladder. J Cardiovasc Pharmacol 2000, 36:S267-S269.

    PubMed  CAS  Google Scholar 

  17. Al-Jiffry BO, Chen JWC, Toouli J, Saccone GTP: Endothelins induce gallbladder contraction independently of elevated blood pressure in-vivo in the Australian possum. J Gastrointest Surg 2002, 6:699–705.

    Article  PubMed  Google Scholar 

  18. McCartney SA, Greaves RRSH, Warner TD, et al.: Endothelin content, expression, and receptor type in normal and diseased human gallbladder. Dig Dis Sci 2002, 47:1786–1792. This study is the first to report levels of ET in inflamed human gallbladder. It demonstrates the expression of mRNA for preproenthelin-1 and 2 and relates the level of ET to the severity of inflammation.

    Article  PubMed  CAS  Google Scholar 

  19. Al-Jiffry BO, Menadue M, Oliver J, et al.: Endothelins in gallbladder tissue are elevated in acalculus acute cholecystitis [abstract]. Gastroenterology, 2002, 122:A440.

    Google Scholar 

  20. Greaves RRSH, O’Donnell LJD, Farthing MJG: Differential effect of prostaglandins on gallstone-free and gallstone-containing human gallbladder. Dig Dis Sci 2000, 45:2376–2381.

    Article  PubMed  CAS  Google Scholar 

  21. Hemming JM, Guarraci FA, Firth TA, et al.: Actions of histamine on muscle and ganglia of the guinea pig gallbladder. Am J Physiology 2000, 279:G622-G630.

    CAS  Google Scholar 

  22. Goldblatt MI, Swartz-Basile DA, Svatek CL, et al.: Decreased gallbladder response in leptin-deficient obese mice. J Gastroenterol Surg 2002, 6:443–444. This interesting study starts to unravel the possible cause of altered gallbladder motility in the obese.

    Google Scholar 

  23. Inkinen J, Sand J, Arvola P, et al.: Direct effect of thyroxine on pig sphincter of Oddi contractility. Dig Dis Sci 2001, 46:182–186. These investigators found that physiologic serum concentrations of the thyroid hormones thyroxine and triiodothyronine decreased acetylcholine- or histamine-induced contraction in pig SO muscle rings. Other hormones (cortisone, estrogen, and testosterone) had no effect on the induced contraction; however, progesterone appeared to have nonspecific actions.

    Article  PubMed  CAS  Google Scholar 

  24. Woods CM, Schloithe AC, Simula ME, et al.: Proximal and distal segments of the possum sphincter of Oddi respond differently to neural and cholecystokinin octapeptide stimulation in vitro. Dig Surg 2000, 17:241–249. CCK-8 application caused a modest reduction in the contraction amplitude and basal tension of muscle strips prepared from the proximal SO but had no effect on the activity of strips from distal ends of the sphincter. There was no difference in the response observed in the pancreatic and biliary sphincter strips. This response was not modified by neural blockade.

    Article  PubMed  CAS  Google Scholar 

  25. Al-Jiffry BO, Jobling JM, Schloithe AC, et al.: Secretin induces variable inhibition of motility in different parts of the Australian possum sphincter of Oddi. Neurogastroenterol Motil 2001, 13:449–455.

    Article  PubMed  CAS  Google Scholar 

  26. Velosy B, Madacsy L, Szepes A, et al.: The effects of somatostatin and octreotide on the human sphincter of Oddi. Eur J Gastroenterol Hepatol 1999, 11:897–901.

    Article  PubMed  CAS  Google Scholar 

  27. Di Francesco V, Mariani A, Angelini G, et al.: Effects of gabexate mesilate, a protease inhibitor, on human sphincter of Oddi motility. Dig Dis Sci 2002, 47:741–745.

    Article  PubMed  Google Scholar 

  28. Koshitani T, Kodama T, Sato H, et al.: A synthetic prostaglandin E-1 analog, alprostadil alfadex, relaxes sphincter of Oddi in humans. Dig Dis Sci 2002, 47:152–156.

    Article  PubMed  CAS  Google Scholar 

  29. Craig AG, Tottrup A, Toouli J, et al.: Relative effects of dihydropyridine L-type calcium channel antagonism on biliary, duodenal, and vascular tissues: an in vivo and in vitro analysis in Australian brush-tailed possum. Dig Dis Sci 2002, 47:2029–2036.

    Article  PubMed  CAS  Google Scholar 

  30. Lee SK, Kim MH, Kim HJ, et al.: Electroacupuncture may relax the sphincter of Oddi in humans. Gastrointest Endosc 2001, 53:211–216. This is a fascinating report on the effect of acupuncture on SO motility. Although the mechanisms are obscure, these results highlight the potential role of the central nervous system in SO motility.

    Article  PubMed  CAS  Google Scholar 

  31. Manning BP, Mawe GM: Tachykinins mediate slow excitatory postsynaptic transmission in guinea pig sphincter of Oddi ganglia. Am J Physiol 2001, 281:G357-G364.

    CAS  Google Scholar 

  32. Patacchini R, Bartho L, De Giorgio R, et al.: Involvement of endogenous tachykinins and CGRP in the motor responses produced by capsaicin in the guinea-pig common bile duct. Naunyn-Schmiedebergs Arch Pharmacol 1999, 360:344–353.

    Article  PubMed  CAS  Google Scholar 

  33. Simula ME, Brookes SJH, Meedeniya ACB, et al.: Distribution of nitric oxide synthase and vasoactive intestinal polypeptide immunoreactivity in the sphincter of Oddi and duodenum of the possum. Cell Tissue Res 2001, 304:31–41.

    Article  PubMed  CAS  Google Scholar 

  34. Vogalis F, Smith TK: Functional innervation of the biliary sphincter of the guinea-pig revealed by anti-autonomic drugs. J Autonom Pharmacol 2000, 20:177–183.

    Article  CAS  Google Scholar 

  35. Shima Y, Mori M, Takakura N, et al.: Continuous monitoring of nitric oxide release induced by cholecystokinin from the choledochal sphincter in guinea pigs. Digestion 2000, 61:135–139.

    Article  PubMed  CAS  Google Scholar 

  36. Konomi H, Woods CM, Meedeniya ACB, et al.: Effects of diaspirin cross-linked hemoglobin on motor function of the duodenum and biliary system in the Australian brush-tailed possum in vivo. J Pharmacol Exp Ther 2001, 296:1067–1073.

    PubMed  CAS  Google Scholar 

  37. Herrmann BW, Cullen JJ, Ledlow A, et al.: The effect of peroxynitrite on sphincter of Oddi motility. J Surg Res 1999, 81:55–58. The complex biologic interactions between reactive molecules like NO, oxygen-derived free radicals, and peroxynitrite that can potentially influence SO motor function are illustrated in this work. Peroxynitrite, produced from the reaction of oxygen-derived free radicals with NO, acted as a smooth muscle relaxant in the SO, and its effect was reversed by hemoglobin. These findings are consistent with hemoglobin-binding peroxynitrite or peroxynitrite-generating NO.

    Article  PubMed  CAS  Google Scholar 

  38. Cullen JJ, Park H, Ephgrave KS, et al.: Lipopolysaccharide temporarily impairs sphincter of Oddi motility. Nitric Oxide 2002, 5:547–554.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of General and Digestive Surgery, Flinders University of South Australia, 5042, Adelaide, Australia

    Gino T. P. Saccone PhD

Authors
  1. Charmaine M. Woods B Biotech (Hons)
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  2. Gary M. Mawe PhD
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  3. Eldon A. Shaffer MD, FRCP, CFACP, FACG
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  4. James Toouli PhD, FRACS
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  5. Gino T. P. Saccone PhD
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Woods, C.M., Mawe, G.M., Shaffer, E.A. et al. Effects of bioactive agents on biliary motor function. Curr Gastroenterol Rep 5, 154–159 (2003). https://doi.org/10.1007/s11894-003-0085-8

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  • DOI: https://doi.org/10.1007/s11894-003-0085-8

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