Santos J, Saperas E, Mourelle M, Antolín M, Malagelada J R
Digestive System Research Unit, Hospital General Vall d'Hebron, Autonomous University of Barcelona, Spain.
Gastroenterology. 1996 Dec;111(6):1465-73. doi: 10.1016/s0016-5085(96)70007-0.
BACKGROUND & AIMS: Intestinal mast cell activity is modulated by the central nervous system, but the mechanisms are not well established. The aim of this study was to investigate whether cerebral thyrotropin-releasing hormone (TRH) activates intestinal mast cells and to elucidate the mechanisms involved, specifically, the contribution of mast cells to vagally stimulated luminal protein release.
In anesthetized rats, mast cell activation was assessed by measuring the release of the specific mucosal rat mast cell protease II (RMCP II) and prostaglandin (PG) D2 into the intestinal lumen. Luminal protein release was measured as an index of epithelial permeability to macromolecules.
Intracisternal injection of the TRH analogue RX 77368 (30 ng) induced a transient increase in intestinal release of RMCP II and PGD2 that was abolished by dox-antrazole. RX 77368-stimulated RMCP II release was also abolished by vagotomy and reduced by atropine by 65%. However, both systemic capsaicin and indo-methacin enhanced RMCP II release. RX 77368-stimulated luminal protein release was abolished by vagotomy and reduced by doxantrazole.
Central vagal activation by TRH stimulates intestinal mast cell secretion, in part via peripheral muscarinic receptors, and is modulated by PGs and capsaicin-sensitive afferent innervation. Intestinal mast cell activation contributes to the TRH analogue-stimulated luminal protein release.
肠道肥大细胞活性受中枢神经系统调节，但其机制尚未完全明确。本研究旨在探讨脑促甲状腺激素释放激素（TRH）是否激活肠道肥大细胞，并阐明其相关机制，特别是肥大细胞对迷走神经刺激引起的肠腔蛋白释放的作用。
在麻醉大鼠中，通过测量特异性黏膜大鼠肥大细胞蛋白酶II（RMCP II）和前列腺素（PG）D2向肠腔的释放来评估肥大细胞的激活。测量肠腔蛋白释放作为上皮对大分子通透性的指标。
脑池内注射TRH类似物RX 77368（30 ng）可引起RMCP II和PGD2肠道释放的短暂增加，多克安唑可消除这种增加。RX 77368刺激的RMCP II释放也可被迷走神经切断术消除，阿托品可使其减少65%。然而，全身应用辣椒素和吲哚美辛均可增强RMCP II的释放。RX 77368刺激的肠腔蛋白释放可被迷走神经切断术消除，多克安唑可使其减少。
TRH引起的中枢迷走神经激活刺激肠道肥大细胞分泌，部分通过外周毒蕈碱受体介导，并受PG和辣椒素敏感传入神经支配的调节。肠道肥大细胞激活有助于TRH类似物刺激的肠腔蛋白释放。
