Role of capsaicin-sensitive sensory nerves in acid-induced bicarbonate secretion in rat stomach.

The effect of capsaicin-sensitive afferent nerves on the alkaline secretory response induced by mucosal acidification was investigated in the ex vivo stomachs of anesthetized rats. The stomach was mounted on a Lucite chamber and perfused with saline (pH 4.5) in the absence of acid secretion (omeprazole pretreatment: 60 mg/kg, intraperitoneal), and luminal pH and transmucosal potential difference (PD) were monitored simultaneously. Under these conditions the gastric mucosa responded to intravenous injection of prostaglandin E2 (PGE2: 300 micrograms/kg) and mucosal acidification (0.2 N HCl for 10 min) by a significant increase of pH with a slight decrease of PD; the HCO3- output was 9.2 +/- 0.7 mumol and 8.4 +/- 0.8 mumol, respectively. The increased pH and HCO3- responses were significantly inhibited by prior administration of indomethacin (5 mg/kg, subcutaneously) or chemical deafferentation following capsaicin injections (total dose: 100 mg/kg, subcutaneously), whereas those induced by PGE2 remained unchanged after either treatment. On the other hand, the mucosal application of capsaicin (0.3-6 mg/ml) increased the luminal pH and HCO3- output in a concentration-related manner, and this action was also significantly attenuated by either indomethacin or chemical deafferentation of capsaicin-sensitive sensory neurons. These results suggest that capsaicin-sensitive sensory nerves may be involved in the mechanism of acid-induced HCO3- secretion in the stomach, in addition to endogenous PGs, and these two pathways may interact somewhere in the stimulatory process.