Grönbech J E, Lacy E R
Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston.
Gastroenterology. 1994 Feb;106(2):440-9. doi: 10.1016/0016-5085(94)90603-3.
BACKGROUND/AIMS: Sensory neurons in the stomach mucosa are closely apposed to mast cells and blood vessels. Mucosal hyperemia, after exposure to capsaicin, is mediated by calcitonin gene-related peptide (CGRP) from these neurons, which also contain substance P (SP). However, the role of this peptide in blood flow regulation remains unclear. Therefore, this study examines the effect of SP on capsaicin-induced mucosal hyperemia and mast cells.
Gastric mucosal blood flow was measured with laser Doppler flow velocimetry in chambered rat stomachs. SP, aprotinin (serine protease inhibitor), and ketotifen (mast cell stabilizer) were infused into the splenic artery of rats. Mast cells were counted by microscopy.
Mucosal exposure to capsaicin (640 mumol/L) evoked a 70% increase in mucosal blood flow, which was abolished by SP, whereas aprotinin infused with SP and pretreatment with ketotifen before SP infusion restored the hyperemic response. Morphometry showed that ketotifen inhibited mast cell degranulation in SP-treated animals. Preservation of mast cells in SP-treated rats was linearly correlated to increased mucosal blood flow after exposure to capsaicin.
These data suggest that SP participates in regulation of gastric mucosal blood flow by activation of mast cells most likely by releasing proteases from mast cells that cleave and inactivate CGRP.
背景/目的：胃黏膜中的感觉神经元与肥大细胞和血管紧密相邻。接触辣椒素后黏膜充血是由这些神经元释放的降钙素基因相关肽（CGRP）介导的，这些神经元还含有P物质（SP）。然而，这种肽在血流调节中的作用仍不清楚。因此，本研究探讨了P物质对辣椒素诱导的黏膜充血和肥大细胞的影响。
用激光多普勒血流仪测量大鼠分隔胃的胃黏膜血流量。将P物质、抑肽酶（丝氨酸蛋白酶抑制剂）和酮替芬（肥大细胞稳定剂）注入大鼠脾动脉。通过显微镜计数肥大细胞。
黏膜接触辣椒素（640μmol/L）使黏膜血流量增加70%，P物质可消除这种增加，而与P物质一起注入抑肽酶以及在注入P物质前用酮替芬预处理可恢复充血反应。形态学测量显示，酮替芬抑制了P物质处理动物的肥大细胞脱颗粒。在P物质处理的大鼠中，肥大细胞的保留与接触辣椒素后黏膜血流量增加呈线性相关。
这些数据表明，P物质可能通过激活肥大细胞来参与胃黏膜血流调节，最有可能是通过释放肥大细胞中的蛋白酶来裂解和灭活CGRP。
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