Hormonal regulation of bicarbonate secretion in the biliary epithelium.
Bicarbonate excretion in bile is a major function of the biliary epithelium. It is driven by the apically located Cl-/HCO3- exchanger which is functionally coupled with a cAMP-dependent Cl- channel (CFTR). A number of hormones and/or neuropeptides with different mechanisms and at different intracellular levels regulate, in concert, the processes underlying bicarbonate excretion in the biliary epithelium. Secretin induces a bicarbonate rich choleresis by stimulating the activity of the Cl-/HCO3- exchanger by cAMP and protein kinase A mediated phosphorylation of CFTR regulatory domain. Protein phosphatase 1/2A are involved in the run-down of secretory stimulus after secretin removal. Acetylcholine potentiates secretin-choleresis by inducing a Ca(++)-calcineurin mediated "sensitization" of adenyl cyclase to secretin. Bombesin and vasoactive intestinal peptide also enhance the Cl-/HCO3- exchanger activity, but the intracellular signal transduction pathway has not yet been defined. Somatostatin and gastrin inhibit basal and/or secretin-stimulated bicarbonate excretion by down-regulating the secretin receptor and decreasing cAMP intracellular levels induced by secretin.
Alvaro
D
D
Department of Clinical Medicine, University of Rome La Sapienza, Italy. alvaro@axrma.uniromal.it
Gigliozzi
A
A
Fraioli
F
F
Romeo
R
R
Papa
E
E
Delle Monache
M
M
Capocaccia
L
L
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D017920:Antiporters / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism*; D001646:Bile / Q000378:metabolism; D001659:Biliary Tract / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D027963:Chloride-Bicarbonate Antiporters; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D004573:Electrolytes / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D006728:Hormones / Q000502:physiology*; D006801:Humans; D017136:Ion Transport
D017920:Antiporters; D001639:Bicarbonates; C505032:CFTR protein, human; D027963:Chloride-Bicarbonate Antiporters; D004573:Electrolytes; D006728:Hormones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000262:Adenylyl Cyclases; D002118:Calcium