title: Immediate neuroendocrine signaling after partial hepatectomy through acute portal hyperpressure and cholestasis.
abstract: OBJECTIVE
  Early neuroendocrine pathways contribute to liver regeneration after partial hepatectomy (PH). We investigated one of these pathways involving acute cholestasis, immediate portal hyperpressure, and arginine vasopressin (AVP) secretion.
  
  
  METHODS
  Surgical procedure (PH, Portal vein stenosis (PVS), bile duct ligation (BDL), spinal cord lesion (SCL)) and treatments (capsaicin, bile acids (BA), oleanolic acid (OA)) were performed on rats and/or wild type or TGR5 (GPBAR1) knock-out mice. In these models, the activation of AVP-secreting supraoptic nuclei (SON) was analyzed, as well as plasma BA, AVP, and portal vein pressure (PVP). Plasma BA, AVP, and PVP were also determined in human living donors for liver transplantation.
  
  
  RESULTS
  Acute cholestasis (mimicked by BDL or BA injection) as well as portal hyperpressure (mimicked by PVS) independently activated SON and AVP secretion. BA accumulated in the brain after PH or BDL, and TGR5 was expressed in SON. SON activation was mimicked by the TGR5 agonist OA and inhibited in TGR5 KO mice after BDL. An afferent nerve pathway also contributed to post-PH AVP secretion, as capsaicin treatment or SCL resulted in a weaker SON activation after PH.
  
  
  CONCLUSIONS
  After PH in rodents, acute cholestasis and portal hypertension, via the nervous and endocrine routes, stimulate the secretion of AVP that may protect the liver against shear stress and bile acids overload. Data in living donors suggest that this pathway may also operate in humans.
authors.affiliation: INSERM U.757, Université Paris Sud, bât. 443, 91405 Orsay, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Doignon
authors.forename: Boris
authors.initials: B
authors.lastname: Julien
authors.forename: Valérie
authors.initials: V
authors.lastname: Serrière-Lanneau
authors.forename: Isabelle
authors.initials: I
authors.lastname: Garcin
authors.forename: Gérard
authors.initials: G
authors.lastname: Alonso
authors.forename: Alexandra
authors.initials: A
authors.lastname: Nicou
authors.forename: François
authors.initials: F
authors.lastname: Monnet
authors.forename: Michelle
authors.initials: M
authors.lastname: Gigou
authors.forename: Lydie
authors.initials: L
authors.lastname: Humbert
authors.forename: Dominique
authors.initials: D
authors.lastname: Rainteau
authors.forename: Daniel
authors.initials: D
authors.lastname: Azoulay
authors.forename: Denis
authors.initials: D
authors.lastname: Castaing
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Gillon
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Duclos-Vallée
authors.forename: Thierry
authors.initials: T
authors.lastname: Tordjmann
mesh_terms: D000328:Adult; D000818:Animals; D001127:Arginine Vasopressin / Q000502:physiology; D001647:Bile Acids and Salts / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D002779:Cholestasis / Q000503:physiopathology; D005260:Female; D006498:Hepatectomy; D006801:Humans; D006975:Hypertension, Portal / Q000503:physiopathology; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009490:Neurosecretory Systems / Q000502:physiology*; D011168:Portal System / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D013495:Supraoptic Nucleus / Q000502:physiology
chemical_list: D001647:Bile Acids and Salts; C513561:Gpbar1 protein, mouse; D043562:Receptors, G-Protein-Coupled; D001127:Arginine Vasopressin