Biogenic amines, such as serotonin, histamine, dopamine, and the catecholamines epinephrine and norepinephrine, regulate a multitude of cellular responses. A great deal of effort has been invested into understanding the effects of these molecules and their corresponding receptor systems on cholangiocyte secretion, apoptosis, and growth. This review summarizes the results of these efforts and highlights the importance of these regulatory molecules on the physiology and pathophysiology of cholangiocytes.
Get full access to this article
View all access options for this article.
References
1.
Alpini G, McGill JM, LaRusso NF. The pathobiology of biliary epithelia. Hepatology35:1256–1268, 2002.
2.
LeSage G, Glaser SS, Gubba S, Robertson WE, Phinizy JL, Lasater J, Rodgers RE, Alpini G. Regrowth of the rat biliary tree after 70% partial hepatectomy is coupled to increased secretin-induced ductal secretion. Gastroenterology111:1633–1644, 1996.
3.
Alvaro D, Mancino MG, Glaser S, Gaudio E, Marzioni M, Francis H, Alpini G. Proliferating cholangiocytes: a neuroendocrine compartment in the diseased liver: Gastroenterology132:415–431, 2007.
4.
Desmet VJ. Vanishing bile duct disorders. Prog Liver Dis10:89–121, 1992.
5.
Annual Report of the U.S. Organ Procurement and Transplantation Network and the Silent Registry for Transplant Recipients: transplant data 1991–2000. Rockville, MD: Department of Health and Human Services Office of Special Programs, 2001.
6.
Tinmouth J, Lee M, Wanless IR, Tsui FW, Inman R, Heathcote EJ. Apoptosis of biliary epithelial cells in primary biliary cirrhosis and primary sclerosing cholangitis. Liver22:228–234, 2002.
7.
Toninello A, Salvi M, Pietrangeli P, Mondovi B. Biogenic amines and apoptosis: minireview article. Amino Acids26:339–343, 2004.
8.
Zeisberger E. Biogenic amines and thermoregulatory changes. Prog Brain Res115:159–176, 1998.
9.
Singewald N, Philippu A. Involvement of biogenic amines and amino acids in the central regulation of cardiovascular homeostasis. Trends Pharmacol Sci17:356–363, 1996.
10.
Medina MA, Urdiales JL, Rodriguez-Caso C, Ramirez FJ, Sanchez-Jimenez F. Biogenic amines and polyamines: similar biochemistry for different physiological missions and biomedical applications. Crit Rev Biochem Mol Biol38:23–59, 2003.
11.
Diksic M, Young SN. Study of the brain serotonergic system with labeled alpha-methyl-L-tryptophan. J Neurochem78:1185–1200, 2001.
12.
Costedio MM, Hyman N, Mawe GM. Serotonin and its role in colonic function and in gastrointestinal disorders. Dis Colon Rectum50:376–378, 2006.
13.
Kroeze WK, Kristiansen K, Roth BL. Molecular biology of serotonin receptors structure and function at the molecular level. Curr Top Med Chem2:507–528, 2002.
14.
Young A, Goodwin GM. Studies on central nervous system serotonin receptors in mood disorders. Ann Acad Med Singapore20:46–50, 1991.
15.
Borman RA, Burleigh DE. Heterogeneity of 5-HT receptors mediating secretion in the human intestine. Ann N Y Acad Sci812:224–225, 1997.
16.
Franks CM, Hardcastle J, Hardcastle PT. Neural involvement in 5-hydroxytryptamine-induced net electrogenic ion secretion in the rat intestine in-vivo. J Pharm Pharmacol48:411–416, 1996.
17.
Li Y, Hao Y, Zhu J, Owyang C. Serotonin released from intestinal enterochromaffin cells mediates luminal non-cholecystokinin-stimulated pancreatic secretion in rats. Gastroenterology118:1197–1207, 2000.
18.
Li Y, Wu XY, Zhu JX, Owyang C. Intestinal serotonin acts as paracrine substance to mediate pancreatic secretion stimulated by luminal factors. Am J Physiol Gastrointest Liver Physiol281:G916–G923, 2001.
19.
Azmitia EC. Modern views on an ancient chemical: serotonin effects on cell proliferation, maturation, and apoptosis. Brain Res Bull56:413–424, 2001.
20.
Balasubramanian S, Paulose CS. Induction of DNA synthesis in primary cultures of rat hepatocytes by serotonin: possible involvement of serotonin S2 receptor. Hepatology27:62–66, 1998.
21.
Papadimas GK, Tzirogiannis KN, Panoutsopoulos GI, Demonakou MD, Skaltsas SD, Hereti RI, Papadopoulou-Daifoti Z, Mykoniatis MG. Effect of serotonin receptor 2 blockage on liver regeneration after partial hepatectomy in the rat liver. Liver Int26:352–361, 2006.
22.
Lesurtel M, Graf R, Aleil B, Walther DJ, Tian Y, Jochum W, Gachet C, Bader M, Clavien PA. Platelet-derived serotonin mediates liver regeneration. Science312:104–107, 2006.
23.
Ruddell RG, Oakley F, Hussain Z, Yeung I, Bryan-Lluka LJ, Ramm GA, Mann DA. A role for serotonin (5-HT) in hepatic stellate cell function and liver fibrosis. Am J Pathol169:861–876, 2006.
24.
Jones EA, Bergasa NV. The pathogenesis and treatment of pruritus and fatigue in patients with PBC. Eur J Gastroenterol Hepatol11:623–631, 1999.
25.
Swain MG, Maric M. Improvement in cholestasis-associated fatigue with a serotonin receptor agonist using a novel rat model of fatigue assessment: Hepatology25:291–294, 1997.
26.
Marzioni M, Glaser S, Francis H, Marucci L, Benedetti A, Alvaro D, Taffetani S, Ueno Y, Roskams T, Phinizy JL, Venter J, Fava G, LeSage GD, Alpini G. Autocrine/paracrine regulation of the growth of the biliary tree by the neuroendocrine hormone serotonin. Gastroenterology128:121–137, 2005.
27.
Parsons ME, Ganellin CR. Histamine and its receptors. Br J Pharmacol147(Suppl 1):S127–S135, 2006.
28.
Hou YF, Zhou YC, Zheng XX, Wang HY, Fu YL, Fang ZM, He SH.Modulation of expression and function of Toll-like receptor 3 in A549 and H292 cells by histamine. Mol Immunol43:1982–1992, 2006.
29.
Jancso G, Santha P, Horvath V, Pierau F. Inhibitory neurogenic modulation of histamine-induced cutaneous plasma extravasation in the pigeon. Regul Pept95:75–80, 2000.
30.
Nguyen T, Shapiro DA, George SR, Setola V, Lee DK, Cheng R, Rauser L, Lee SP, Lynch KR, Roth BL, O’Dowd BF. Discovery of a novel member of the histamine receptor family. Mol Pharmacol59: 427–433, 2001.
31.
Repka-Ramirez MS. New concepts of histamine receptors and actions. Curr Allergy Asthma Rep3:227–231, 2003.
32.
Dickenson JM. Stimulation of protein kinase B and p70 S6 Kinase by the histamine H1 receptor in DDT1MF-2 smooth muscle cells. Br J Pharmacol135:19 67–1976, 2002.
33.
Mitsuhashi M, Mitsuhashi T, Payan D. Multiple signaling pathways of histamine H2 receptors (Identification of an H2 receptor-dependent Ca2+ mobilization pathway in human HL-60 promyelocytic leukemia cells). J Biol Chem264:18356–18362, 1989.
34.
Lovenberg TW, Pyati J, Chang H, Wilson SJ, Erlander MG. Cloning of rat histamine H(3) receptor reveals distinct species pharmacological profiles. J Pharmacol Exp Ther293:771–778, 2000.
35.
Lovenberg TW, Roland BL, Wilson SJ, Jiang X, Pyati J, Huvar A, Jackson MR, Erlander MG. Cloning and functional expression of the human histamine H3 receptor. Mol Pharmacol55:1101–1107, 1999.
36.
Liu C, Ma X, Jiang X, Wilson SJ, Hofstra CL, Blevitt J, Pyati J, Li X, Chai W, Carruthers N, Lovenberg TW. Cloning and pharmacological characterization of a fourth histamine receptor (H(4)) expressed in bone marrow. Mol Pharmacol59:420–426, 2001.
37.
Udenfriend S. Amino acid decarboxylation steps in the biosynthesis of norepinephrine, serotonin, and histamine. Vitam Horm22:445–450, 1964.
38.
Jutel M, Blaser K, Akdis CA. Histamine in allergic inflammation and immune modulation. Int Arch Allergy Immunol137:82–92, 2005.
39.
Brown RE, Stevens DR, Haas HL. The physiology of brain histamine. Prog Neurobiol63:637–672, 2001.
40.
Prinz C, Zanner R, Gerhard M, Mahr S, Neumayer N, Hohne-Zell B, Gratzl M. The mechanism of histamine secretion from gastric enterochromaffin-like cells. Am J Physiol277:C845–C855, 1999.
41.
Wang LD, Hoeltzel M, Butler K, Hare B, Todisco A, Wang M, Del Valle J. Activation of the human histamine H2 receptor is linked to cell proliferation and c-fos gene transcription. Am J Physiol273:C2037–C2045, 1997.
42.
Rizell M, Hellstrand K, Lindner P, Naredi P. Monotherapy with histamine dihydrochloride suppresses in vivo growth of a rat sarcoma in liver and subcutis. Anticancer Res22:1943–1948, 2002.
43.
Cricco G, Martin G, Medina V, Nunez M, Mohamad N, Croci M, Crescenti E, Bergoc R, Rivera E. Histamine inhibits cell proliferation and modulates the expression of Bcl-2 family proteins via the H2 receptor in human pancreatic cancer cells. Anticancer Res26:4443–4450, 2006.
44.
Medina V, Cricco G, Nunez M, Martin G, Mohamad N, Correa-Fiz F, Sanchez-Jimenez F, Bergoc R, Rivera ES. Histamine-mediated signaling processes in human malignant mammary cells. Cancer Biol Ther5: 1462–1471, 2006.
45.
Grandi D, Schunack W, Morini G. Epithelial cell proliferation is promoted by the histamine H(3) receptor agonist (R)-alpha-methylhistamine throughout the rat gastrointestinal tract. Eur J Pharmacol538: 141–147, 2006.
46.
Morini G, Grandi D, Schunack W. Ligands for histamine H(3) receptors modulate cell proliferation and migration in rat oxyntic mucosa. Br J Pharmacol137:237–244, 2002.
47.
Adachi N, Liu K, Motoki A, Nishibori M, Arai T. Suppression of ischemia/reperfusion liver injury by histamine H4 receptor stimulation in rats. Eur J Pharmacol544:181–187, 2006.
48.
Hiraga N, Adachi N, Liu K, Nagaro T, Arai T. Suppression of inflammatory cell recruitment by histamine receptor stimulation in ischemic rat brains. Eur J Pharmacol557:236–244, 2006.
Ehrenpreis S, Kimura I, Kobayashi T, Kimura M. Histamine release as the basis for morphine action on bile duct and sphincter of Oddi. Life Sci40:1695–1698, 1987.
51.
Jones RS, Grossman MI. Choleretic effects of secretin and histamine in the dog. Am J Physiol217:532–535, 1969.
52.
Jones RS, Grossman MI. Dose-response relationships of the choleretic effect of histamine. Am J Physiol216:335–339, 1969.
53.
Francis H, Franchitto A, Ueno Y, Glaser S, DeMorrow S, Venter J, Gaudio E, Alvaro D, Fava G, Marzioni M, Vaculin B, Alpini G. H3 histamine receptor agonist inhibits cholangiocyte growth of BDL rats by downregulation of the cAMP-dependent PKA/ERK1/2 /ELK-1pathway. Lab Invest87:473–487, 2007.
54.
Francis H, Taffetani S, Glaser S, Venter J, Phinizy JL, Reichenbach R, Fava G, Alvaro D, Marucci L, Benedetti A, Marzioni M, Alpini G. Histamine stimulates cholangiocyte proliferation through transduction pathways involving the H1 and H2 histamine receptor subtypes. Gastroenterology126:AT925, 2004.
55.
Callier S, Snapyan M, Le Crom S, Prou D, Vincent JD, Vernier P. Evolution and cell biology of dopamine receptors in vertebrates. Biol Cell95:489–502, 2003.
56.
Enjalbert A. Multiple transduction mechanisms of dopamine, somatostatin and angiotensin II receptors in anterior pituitary cells. Horm Res31:6–12, 1989.
57.
Carvey PM, Punati A, Newman MB. Progressive dopamine neuron loss in Parkinson’s disease: the multiple hit hypothesis: Cell Transplant15: 239–250, 2006.
58.
Willner P. The dopamine hypothesis of schizophrenia: current status, future prospects. Int Clin Psychopharmacol12:297–308, 1997.
59.
Bressan RA, Crippa JA. The role of dopamine in reward and pleasure behaviour–review of data from preclinical research. Acta Psychiatr Scand Suppl:14–21, 2005.
60.
Glaser S, Alvaro D, Roskams T, Phinizy JL, Stoica G, Francis H, Ueno Y, Barbaro B, Marzioni M, Mauldin J, Rashid S, Mancino MG, LeSage G, Alpini G. Dopaminergic inhibition of secretin-stimulated choleresis by increased PKC-gamma expression and decrease of PKA activity. Am J Physiol Gastrointest Liver Physiol284:G683–G694, 2003.
61.
Glaser S, Benedetti A, Marucci L, Alvaro D, Baiocchi L, Kanno N, Caligiuri A, Phinizy JL, Chowdhury U, Papa E, LeSage G, Alpini G. Gastrin inhibits cholangiocyte growth in bile duct-ligated rats by interaction with cholecystokinin-B/Gastrin receptors via D-myoinositol 1,4,5-triphosphate-, Ca(2+)-, and protein kinase C alpha-dependent mechanisms. Hepatology32:17–25, 2000.
62.
Glaser SS, Rodgers RE, Phinizy JL, Robertson WE, Lasater J, Caligiuri A, Tretjak Z, LeSage GD, Alpini G. Gastrin inhibits secretin-induced ductal secretion by interaction with specific receptors on rat cholangiocytes. Am J Physiol273:G1061–G1070, 1997.
63.
LeSage G, Glaser S, Alpini G. Regulation of cholangiocyte proliferation. Liver21:73–80, 2001.
64.
Francis H, Glaser S, Ueno Y, Lesage G, Marucci L, Benedetti A, Taffetani S, Marzioni M, Alvaro D, Venter J, Reichenbach R, Fava G, Phinizy JL, Alpini G. cAMP stimulates the secretory and proliferative capacity of the rat intrahepatic biliary epithelium through changes in the PKA/Src/MEK/ERK1/2 pathway. J Hepatol41:528–537, 2004.
65.
LeSage GD, Marucci L, Alvaro D, Glaser SS, Benedetti A, Marzioni M, Patel T, Francis H, Phinizy JL, Alpini G. Insulin inhibits secretin-induced ductal secretion by activation of PKC alpha and inhibition of PKA activity. Hepatology36:641–651, 2002.
66.
LeSage GD, Alvaro D, Glaser S, Francis H, Marucci L, Roskams T, Phinizy JL, Marzioni M, Benedetti A, Taffetani S, Barbaro B, Fava G, Ueno Y, Alpini G. Alpha-1 adrenergic receptor agonists modulate ductal secretion of BDL rats via Ca(2+)- and PKC-dependent stimulation of cAMP. Hepatology40:1116–1127, 2004.
67.
Flatmark T. Catecholamine biosynthesis and physiological regulation in neuroendocrine cells. Acta Physiol Scand168:1–17, 2000.
68.
Kobayashi K. Role of catecholamine signaling in brain and nervous system functions: new insights from mouse molecular genetic study. J Investig Dermatol Symp Proc6:115–121, 2001.
69.
Arun CP. Fight or flight, forbearance and fortitude: the spectrum of actions of the catecholamines and their cousins. Ann N Y Acad Sci1018:137–140, 2004.
70.
Rang H, Dale M, Ritter J, Moore P. Pharmacology. New York: Elsevier Churchill Livingstone, 2003.
71.
Beckh K, Arnold R. Regulation of bile secretion by sympathetic nerves in perfused rat liver. Am J Physiol261:G775–G780, 1991.
72.
Krell H, Jaeschke H, Pfaff E. Regulation of canalicular bile formation by alpha-adrenergic action and by external ATP in the isolated perfused rat liver. Biochem Biophys Res Commun131:139–145, 1985.
