Role of capsaicin-sensitive afferent neurons in alkaline secretory response to luminal acid in the rat duodenum

Abstract

The role of capsaicin-sensitive afferent neurons in acid-induced HCO3− secretion was investigated in the duodenum of anesthetized rats. The proximal duodenum was perfused with saline (pH 4.5), the pH of perfusate and the transmucosal potential differences were continuously monitored, and HCO3− output was determined by pH change. Under these conditions, duodenal pH, potential difference, and HCO3− output were significantly increased in response to IV injection of prostaglandin E2 (300 μg/kg) and luminal acidification (10 mmol/L HCl, 10 minutes). These responses induced by luminal acid were significantly attenuated by SC pretreatment with indomethacin (5 mg/kg), preexposure of the mucosa to lidocaine (4%, 15 minutes), functional ablation of capsaicin-sensitive afferent neurons, or even prior application of capsaicin (6 mg/mL, 30 minutes) to the duodenum. Although capsaicin application by itself (0.3–6 mg/mL) produced a concentration-dependent increase of HCO3− output, this effect was significantly reduced by lidocaine, indomethacin, or chemical deafferentation and exhibited a tachyphylaxis after repeated application at a high concentration (6 mg/mL). Neither of these treatments significantly affected the HCO3− response induced by prostaglandin E2. It was concluded that stimulation of capsaicinsensitive afferent neurons increased duodenal HCO3− secretion and that these neurons may be involved in the mechanism of HCO3− response induced by luminal acid in the duodenum.