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The G-protein on cholesterol-rich membrane microdomains mediates mucosal sensing of short-chain fatty acid and secretory response in rat colon

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Title: The G-protein on cholesterol-rich membrane microdomains mediates mucosal sensing of short-chain fatty acid and secretory response in rat colon
Authors: Yajima, T. Browse this author
Inoue, R. Browse this author
Yajima, M. Browse this author
Tsuruta, T. Browse this author
Karaki, S. Browse this author
Hira, T. Browse this author
Kuwahara, A. Browse this author
Keywords: GPR 43
G α_[q/11]
lipid lafts
mucosa-submucosa preparation
propionate
short-circuit current
Issue Date: Nov-2011
Publisher: Blackwell Publishing
Journal Title: Acta Physiologica
Volume: 203
Issue: 3
Start Page: 381
End Page: 389
Publisher DOI: 10.1111/j.1748-1716.2011.02331.x
PMID: 21649864
Abstract: Aim: Short-chain fatty acids (SCFA) stimulate colonic contraction and secretion, which are mediated by an enteric reflex via a mucosal sensing and cholinergic mechanisms. The involvement of G-protein signal transduction was examined in the secretory response to luminal propionate sensing in rat distal colon. Methods: Mucosa-submucosa and mucosa preparations were used to measure short-circuit current (I_[sc]) and acetylcholine (ACh) release respectively. Cholesterol-rich membrane microdomains, lipid rafts/caveolae, were fractionated using a sucrose-gradient ultra-centrifugation after detergent-free extraction of the isolated colonic crypt. Results: Luminal addition of methyl-β-cyclodextrin (10 mM) and mastoparan (30 μM), lipid rafts/caveolae disruptors, significantly inhibited luminal propionate-induced (0.5 mM) increases in I_[sc], but did not affect increases in I_[sc] induced by serosal ACh (0.05 mM) or electrical field stimulation (EFS). Luminal addition of YM-254890 (10 μM), a Gα_[q/11]-selective inhibitor, markedly inhibited propionate-induced increase in I_[sc], but did not affect I_[sc] responses to ACh and EFS. Both methyl-β-cyclodextrin and YM-254890 significantly inhibited luminal propionate-induced non-neuronal release of ACh from colonocytes. Real-time PCR demonstrated that in mRNA expression of SCFA receptors, GPR 43 was far higher than that of GPR41 in the colon. Western blotting analysis revealed that the cholesterol-rich membrane microdomains that fractionated from colonic crypt cells were associated with caveolin-1, flotillin-1 and Gα_[q/11], but not GPR43. Uncoupling of Gα_[q/11] from flotillin-1 in lipid rafts occurred under desensitization of the I_[sc] response to propionate. Conclusions: These data demonstrate that the secretory response to luminal propionate in rat colon is mediated by G-protein on cholesterol-rich membrane microdomains, provably via Gα_[q/11].
Rights: Author Posting. © The Authors 2011. This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in Acta Physiologica, 203(3), 381–389. http://dx.doi.org/10.1111/j.1748-1716.2011.02331.x
Type: article (author version)
URI: http://hdl.handle.net/2115/50370
Appears in Collections:創成研究機構 (Creative Research Institution) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 矢島 高二

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