Abstract
We compared the HCO3 − secretory response to capsaicin and mucosal acidification in rat duodenums, especially the relation to vanilloid receptor type 1 (VR1). A proximal duodenal loop was perfused with saline, and the HCO3 − secretion was measured at pH 7.0 using a pH-stat method and by adding 10 mM HCl. The secretion was stimulated by exposing the loop to capsaicin (0.03–0.3 mg/ml) or 10 mM HCl for 10 min. Indomethacin subcutaneously or ruthenium red intravenously, a nonspecific VR1 antagonist, was given 60 or 10 min, respectively, before exposure to capsaicin or acid, while l-NAME was given intravenously 3 hr before these treatments. Capsazepine, another VR1 antagonist, was coapplied to the loop for 10 min with capsaicin or acid. Luminal application of capsaicin increased the secretion of HCO3 − in a dose-dependent manner; this effect was markedly attenuated by chemical ablation of capsaicin-sensitive afferent neurons (CSN) as well as pretreatment with ruthenium red or capsazepine, and significantly mitigated by indomethacin or l-NAME (in an l-arginine-sensitive manner). The HCO3 − secretion was also stimulated by mucosal acidification, and this response was attenuated by both capsaicin pretreatment, indomethacin and l-NAME, but not ruthenium red or capsazepine. Mucosal application of capsaicin as well as acid increased the mucosal PGE2 content, and these effects were both significantly attenuated by indomethacin and l-NAME. These results suggest that both capsaicin and acid cause the CSN-dependent increase in duodenal HCO3 − secretion mediated by NO and PG, yet the mode of their action differs in terms of the ruthenium red or capsazepine sensitivity. Although luminal H+ plays a modulatory role in duodenal HCO3 − secretion, it is unlikely that the action results from the interaction of H+ with the ruthenium red- or capsazepine-sensitive site of VR1.
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Kagawa, S., Aoi, M., Kubo, Y. et al. Stimulation by Capsaicin of Duodenal HCO3 − Secretion via Afferent Neurons and Vanilloid Receptors in Rats: Comparison with Acid-Induced HCO3 − Response. Dig Dis Sci 48, 1850–1856 (2003). https://doi.org/10.1023/A:1025480003388
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DOI: https://doi.org/10.1023/A:1025480003388