Sensory pathways and cyclooxygenase regulate mucus gel thickness in rat duodenum

We previously showed that the duodenal hyperemic response to acid occurs th rough activation of capsaicin-sensitive afferent nerves with subsequent rel ease of vasodilatory substances such as calcitonin gene-related peptide (CG RP) and nitric oxide. We then tested the hypothesis that similar factors re gulate duodenal mucus gel thickness. Gel thickness was optically measured u sing in vivo microscopy in anesthetized rats. Duodenal mucosae were superfu sed with pH 7.0 buffer with vanilloid receptor agonist capsaicin, bradykini n, or PGE(2) injection or were challenged with pH 2.2 solution, with or wit hout the vanilloid antagonist capsazepine, human CGRP-(8-37), N-G-nitro-L-a rginine methyl ester, and indomethacin. Other rats underwent sensory ablati on with high-dose capsaicin pretreatment. Acid, bradykinin, capsaicin, and PGE(2) all quickly thickened the gel. Antagonism of vanilloid and CGRP rece ptors, inhibition of nitric oxide synthase, and sensory deafferentation del ayed gel thickening, suggesting that the capsaicin pathway mediated the ini tial burst of mucus secretion that thickened the gel. Indomethacin abolishe d gel thickening due to acid, bradykinin, and capsaicin. Inhibition of gel thickening by indomethacin in response to multiple agonists suggests that c yclooxygenase activity is essential for duodenal gel thickness regulation. Duodenal afferent neural pathways play an important role in the modulation of cyclooxygenase-mediated physiological control of gel thickness.