Dopamine enhances duodenal epithelial permeability via the dopamine D₅ receptor in rodent

The intestinal barrier is made up of epithelial cells and intercellular junctional complexes to regulate epithelial ion transport and permeability. Dopamine (DA) is able to promote duodenal epithelial ion transport through D1-like receptors, which includes subtypes of D₁ (D₁ R) and D₅ (D₅ R), but whether D1-like receptors influence the duodenal permeability is unclear.

FITC-dextran permeability, short-circuit current (I_SC ), Western blot, immunohistochemistry and ELISA were used in human D₅ R transgenic mice and hyperendogenous enteric DA (HEnD) rats in this study.

Dopamine induced a downward deflection in I_SC and an increase in FITC-dextran permeability of control rat duodenum, which were inhibited by the D1-like receptor antagonist, SCH-23390. However, DA decreased duodenal transepithelial resistance (TER), an effect also reversed by SCH-23390. A strong immunofluorescence signal for D₅ R, but not D₁ R, was observed in the duodenum of control rat. In human D₅ R knock-in transgenic mice, duodenal mucosa displayed an increased basal I_SC with high FITC-dextran permeability and decreased TER with a lowered expression of tight junction proteins, suggesting attenuated duodenal barrier function in these transgenic mice. D₅ R knock-down transgenic mice manifested a decreased basal I_SC with lowered FITC-dextran permeability. Moreover, an increased FITC-dextran permeability combined with decreased TER and tight junction protein expression in duodenal mucosa were also observed in HEnD rats.

This study demonstrates, for the first time, that DA enhances duodenal permeability of control rat via D₅ R, which provides new experimental and theoretical evidence for the influence of DA on duodenal epithelial barrier function.