Non-neuronal, but atropine-sensitive ileal contractile responses to short-chain fatty acids: age-dependent desensitization and restoration under inflammatory conditions in mice.
Non-neuronal, but atropine-sensitive ileal contractile responses to short-chain fatty acids: age-dependent desensitization and restoration under inflammatory conditions in mice.
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DOI：
10.14814/phy2.12759
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发表时间：
2016-04
影响因子：
2.5
通讯作者：
Iwanaga T
中科院分区：
文献类型：
--
作者：
Yajima M;Kimura S;Karaki S;Nio-Kobayashi J;Tsuruta T;Kuwahara A;Yajima T;Iwanaga T
肠上皮细胞感知短链脂肪酸（SCFA）以分泌非神经元乙酰胆碱（ACh）。然而，管腔 SCFA 和上皮 ACh 在正常和病理条件下的作用仍然未知。我们检查了不同年龄的 SCFA 的回肠收缩反应及其在炎症条件下的粘膜胆碱能变化。使用等渗传感器比较 1 日龄幼犬和 7 周龄小鼠对 SCFA 的回肠收缩反应，并分析 7 周龄小鼠腹膜内注射脂多糖 (LPS) 的反应。使用实时定量 RT-PCR 测量 SCFA 激活游离脂肪酸受体、乙酰胆碱酯酶 (AChE)、胆碱乙酰转移酶 (Chat) 和胆碱转运蛋白样蛋白 4 (CTL4) 的 mRNA 表达水平。通过组织化学和光学酶法分析AChE。所有 1 日龄幼犬均出现对短链脂肪酸阿托品敏感的回肠收缩反应，但在断奶期后通常会脱敏。这些收缩反应不受河豚毒素抑制，并且当粘膜层被刮掉时也不会出现。 7 周龄小鼠的收缩脱敏在 AChE 抑制剂 eserine 存在下被取消，这与断奶后 AChE 活性增加一致。 LPS 可恢复成年小鼠回肠对 SCFA 的收缩，从而显着增加 Chat 和 CTL4 的上皮 mRNA 表达。对 SCFA 的阿托品敏感回肠收缩反应持续发生在新生儿期，并且在发育阶段随着绒毛粘膜中 AChE 表达上调而脱敏，但在炎症条件下可能通过上皮 ACh 的释放而恢复。
Intestinal epithelial cells sense short‐chain fatty acids (SCFAs) to secrete non‐neuronal acetylcholine (ACh). However, the roles of luminal SCFAs and epithelial ACh under normal and pathological conditions remain unknown. We examined ileal contractile responses to SCFAs at different ages and their mucosal cholinergic alterations under inflammatory conditions. Ileal contractile responses to SCFAs in 1‐day‐old pups to 7‐week‐old mice were compared using an isotonic transducer, and responses to an intraperitoneal injection of lipopolysaccharide (LPS) were analyzed in 7‐week‐old mice. The mRNA expression levels of a SCFA activate free fatty acid receptor, acetylcholinesterase (AChE), choline acetyltransferase (Chat), and choline transporter‐like protein 4 (CTL4) were measured using real‐time quantitative RT‐PCR. AChE was analyzed by histochemical and optical enzymatic assays. Atropine‐sensitive ileal contractile responses to SCFAs occurred in all 1‐day‐old pups, but were frequently desensitized after the weaning period. These contractile responses were not inhibited by tetrodotoxin and did not appear when the mucosal layer had been scraped off. Contractile desensitization in 7‐week‐old mice was abolished in the presence of the AChE inhibitor, eserine, which was consistent with increased AChE activity after weaning. Ileal contractions to SCFAs in adult mice were restored by LPS, which significantly increased the epithelial mRNA expression of Chat and CTL4. Atropine‐sensitive ileal contractile responses to SCFAs constitutively occur in the newborn period, and are desensitized during developmental stages following the up‐regulated expression of AChE in the villous mucosa, but are restored under inflammatory conditions possibly via the release of epithelial ACh.