Stimulation of synthesis and release of brain-derived neurotropic factor from intestinal smooth muscle cells by substance P and pituitary adenylate cyclase-activating peptide.
Stimulation of synthesis and release of brain-derived neurotropic factor from intestinal smooth muscle cells by substance P and pituitary adenylate cyclase-activating peptide.
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DOI：
10.1111/nmo.12604
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发表时间：
2015-08
影响因子：
3.5
通讯作者：
Grider JR
中科院分区：
文献类型：
--
作者：
Al-Qudah M;Alkahtani R;Akbarali HI;Murthy KS;Grider JR
脑源性神经营养因子(BDNF)是一种存在于肠道中的神经营养因子，它参与肠道神经元的存活和生长，增强肠道回路，刺激肠道蠕动和推进。以往的研究主要集中在神经和粘膜BDNF的作用上。BDNF在肠道中的表达、释放及其与肠神经肽的相互作用在肠道中尚未见报道。用免疫印迹和酶联免疫吸附试验检测P物质和垂体腺苷环化酶激活肽(PACAP)对培养的兔肠纵行肌细胞表达和分泌脑源性神经营养因子的影响。逆转录-聚合酶链式反应检测脑源性神经营养因子基因的表达。BNDF蛋白和mRNA在纵肌层的表达高于环肌层。PACAP和P物质可增加培养的纵行肌细胞BDNF蛋白和mRNA的表达。PACAP和P物质也能刺激培养的纵行肌细胞分泌BDNF。细胞内钙离子与BAPTA的络合作用可阻止P物质诱导的BDNFmRNA和蛋白表达的增加以及P物质诱导的BDNF的分泌。已知的神经肽存在于支配纵层的肠神经细胞中，增加血管内皮细胞BDNF的mRNA和蛋白的表达，并刺激BDNF的释放。考虑到BDNF增强平滑肌收缩的能力，这种自分泌环路可能部分解释了炎症性肠病中纵肌的特征收缩亢进。
Brain-derived neurotrophic factor (BDNF) is a neurotrophin present in the intestine where it participates in survival and growth of enteric neurons, augmentation of enteric circuits, and stimulation of intestinal peristalsis and propulsion. Previous studies largely focused on the role of neural and mucosal BDNF. The expression and release of BDNF from intestinal smooth muscle and the interaction with enteric neuropeptides has not been studied in gut. The expression and secretion of BDNF from smooth muscle cultured from rabbit longitudinal intestinal muscle in response to substance P and pituitary adenylate cyclase activating peptide (PACAP) was measured by western blot and ELISA. BDNF mRNA was measured by rt-PCR. The expression of BNDF protein and mRNA was greater in smooth muscle cells from the longitudinal muscle than from circular muscle layer. PACAP and substance P increased the expression of BDNF protein and mRNA in cultured longitudinal smooth muscle cells. PACAP and substance P also stimulated the secretion of BDNF from cultured longitudinal smooth muscle cells. Chelation of intracellular calcium with BAPTA prevented substance P-induced increase in BDNF mRNA and protein expression as well as substance P-induced secretion of BDNF. Neuropeptides known to be present in enteric neurons innervating the longitudinal layer increase the expression of BDNF mRNA and protein in smooth muscle cells and stimulate the release of BDNF. Considering the ability of BDNF to enhance smooth muscle contraction, this autocrine loop may partially explain the characteristic hypercontractility of longitudinal muscle in inflammatory bowel disease.