Neurotransmitters and cytokines can modulate the bile duct proliferation through c-AMP /PKA/ERK pathway. Dopamine may bind with dopamine type two receptor(D2R) to increase PKC-γ expression and decrease PKA activity, them, it could inhibit bile duct proliferation.
We used 6-hydroxyldopamine(6-OHDA) as bioaminergic depletor to lower dopamine level and evaluated that whether reduced endogenous dopamine level may influence the bile duct proliferation in rat bile duct ligated animal model. Previously, our laboratory found bile duct proliferation of Wistar-Kyoto rats(WKY) rats was much higher than Spontaneously hypertensive rat(SHR) rats after 3 weeks bile duct ligation (BDL) . Cholangiocyte expressed D2R and its expression was markedly upregulated after BDL. Our goal in this study was to find out that D2R regulate the cholangiocyte proliferation between SHR and WKY rats after BDL.
Our results in immunohistochemistry(IHC), expression of D2R was upregulated after BDL and much higher after BDL + 6-ODDA (sympathetic inhibitor) and its expression of SHR rats was more than WKY rats. In Masson trichrome stain for collagen, the expression of bile duct proliferation in WKY was much more than SHR after BDL . Bile duct proliferation was ugregulated after 6-OHDA used. D2R would combine with dopamine to inhibit bile duct proliferation .After 6-OHDA injection , the D2R with decreased dopamine could not inhibit bile duct proliferation .So bile duct proliferation upregulated . Our finding suggested that D2R play a critical role in modulated bile duct proliferation after BDL, especially in hypertensive rats (SHR).
