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Differential stimulation of duodenal HCO 3 − secretion by luminal fatty acids
Author(s) -
Akiba Yasutada,
Inoue Takuya,
Higashiyama Masaaki,
Rudenkyy Sergiv,
Iwamoto Ken-ichi,
Kuwahara Atsukazu,
Kaunitz Jonathan D
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1154.2
Subject(s) - agonist , endocrinology , free fatty acid receptor 1 , medicine , chemistry , receptor , propionate , monocarboxylate transporter , fatty acid , biology , biochemistry , transporter , gene
Luminal nutrients enhance mucosal defenses via gut hormone release. We examined the effects of long‐chain (LCFA) or short‐chain fatty acid (SCFA) receptor agonists on duodenal HCO 3 − secretion (DBS). We measured DBS with pH and CO 2 electrodes in a perfused duodenal loop in anesthetized rats. Acetate or propionate, GPR43 agonist phenylacetamide 1 (PA1) or GPR40 agonist GW9508 was luminally perfused +/− iv dipeptidyl peptidase 4 inhibitor NVP728 or hormone receptor antagonist. LCFA receptor GPR40 and SCFA receptors GPR41/43 were expressed in the duodenal enteroendocrine cells. Luminal perfusion of acetate or propionate similarly increased DBS, enhanced by NVP728, while increasing GLP‐2 release in portal blood. Acetate‐induced DBS was reduced by the monocarboxylate transporter inhibitor, suggesting the acetate absorption‐mediated and GLP‐2‐mediated DBS. PA1 dose‐dependently increased DBS, unaffected by NVP728 or CCK‐A receptor antagonist, but inhibited by atropine or 5‐HT4 antagonist. The GPR40 agonist GW9508 increased DBS with GLP‐2 release, enhanced by NVP728. Activation of GPR40 by LCFA and possibly GPR41 by SCFA increases DBS via GLP‐2 release, whereas GPR43 activation stimulates DBS via muscarinic and 5‐HT4 receptor activation. The presence of fatty acid sensing in the duodenal mucosal defenses may be implicated in the pathogenesis of functional dyspepsia syndromes. VA Merit Review, R01 DK54221