title: Dopamine D1 receptors mediate dopamine-induced duodenal epithelial ion transport in rats.
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 (ISC), 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 ISC 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 ISC (△ISC) in a dose-dependent manner. D1 agonist, SKF38393, mimicked the effect of DA on the ISC. The clear immunoreactivity of D1 subtype D5 (D1b) 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 △ISC. 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 △ISC was remarkably inhibited by apical administration of K(+) channel blockers, Ba(2+) 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.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Science, Capital Medical University, Beijing, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Feng
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Li
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.forename: Li-Fei
authors.initials: LF
authors.lastname: Zheng
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Zhang
authors.forename: Rui-Fang
authors.initials: RF
authors.lastname: Fan
authors.forename: Jin
authors.initials: J
authors.lastname: Song
authors.forename: Feng
authors.initials: F
authors.lastname: Hong
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jin-Xia
authors.initials: JX
authors.lastname: Zhu
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D004553:Electric Conductivity; D007097:Imines / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D001552:Benzazepines; D001639:Bicarbonates; D007097:Imines; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C014925:RMI 12330A; D000242:Cyclic AMP; D011188:Potassium; D004298:Dopamine