大鼠中的多巴胺D1受体可介导多巴胺诱导性十二指肠上皮离子转运

Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing 10069, China

Abstract

Dopamine (DA) is synthesized in gastrointestinal epithelial cells and performs important regulatory effects on the duodenal mucosa. However, the underlying mechanism remains largely unknown. The present study investigated the effect of DA on the duodenal epithelial ion transport in rats by means of short-circuit current (I_SC), real-time pH titration, enzyme-linked immunosorbent assay, and immunohistochemistry. The results indicate that basolateral, but not apical, application of DA induced a concentration-dependent I_SC downward deflection with an apparent IC₅₀ of 5.34 μmol/L. Basolateral application of dopaminergic receptor D1 (D1) antagonist, SCH-23390, inhibited DA-induced change in I_SC (I_SC) in a dose-dependent manner. D1 agonist, SKF38393, mimicked the effect of DA on the I_SC. The clear immunoreactivity of D1 subtype D₅ (D _1b) was at the both apical and basolatoral sides of Brunner's glands and intestinal crypts. Basolateral pretreatment with adenylate cyclase inhibitor, MDL12330A, significantly inhibited DA- and forskolin-induced I _SC. DA and SKF38393 increased the level of intracellular cyclic adenosine monophosphate (cAMP) from 1.55 ± 0.11 to 2.07 ± 0.11 and 5.91 ± 0.25 pmol/L·mg^-1, respectively. Furthermore, the serosal DA-induced I_SC was remarkably inhibited by apical administration of K⁺ channel blockers, Ba²⁺ and tetraethylammonium, but not by Cl^- channel blockers. Serosal DA and D1 agonist did not affect duodenal HCO₃ ^- secretion. In conclusion, the present results demonstrate that serosal DA is able to promote rat duodenal epithelial K⁺ secretion, not HCO₃ ^-secretion through D1-mediated and cAMP-dependent pathway. The study provides a new insight in the modulation of DA on the ion transport of duodenal epithelia in rats.