Substance P Attenuates Gastric Mucosal Hyperemia After Stimulation of Sensory Neurons in the Rat Stomach

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.

Methods: 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.

Results: 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.

Conclusions: 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.