Sensory pathways and cyclooxygenase regulate mucus gel thickness in rat duodenum.
We previously showed that the duodenal hyperemic response to acid occurs through activation of capsaicin-sensitive afferent nerves with subsequent release of vasodilatory substances such as calcitonin gene-related peptide (CGRP) and nitric oxide. We then tested the hypothesis that similar factors regulate duodenal mucus gel thickness. Gel thickness was optically measured using in vivo microscopy in anesthetized rats. Duodenal mucosae were superfused with pH 7.0 buffer with vanilloid receptor agonist capsaicin, bradykinin, or PGE(2) injection or were challenged with pH 2.2 solution, with or without the vanilloid antagonist capsazepine, human CGRP-(8-37), N(G)-nitro-L-arginine methyl ester, and indomethacin. Other rats underwent sensory ablation with high-dose capsaicin pretreatment. Acid, bradykinin, capsaicin, and PGE(2) all quickly thickened the gel. Antagonism of vanilloid and CGRP receptors, inhibition of nitric oxide synthase, and sensory deafferentation delayed gel thickening, suggesting that the capsaicin pathway mediated the initial burst of mucus secretion that thickened the gel. Indomethacin abolished gel thickening due to acid, bradykinin, and capsaicin. Inhibition of gel thickening by indomethacin in response to multiple agonists suggests that cyclooxygenase 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.
Akiba
Y
Y
CURE: Digestive Diseases Research Center, Department of Medicine, School of Medicine, University of California, Los Angeles, California 90073, USA.
Furukawa
O
O
Guth
P H
PH
Engel
E
E
Nastaskin
I
I
Kaunitz
J D
JD
D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage; D002211:Capsaicin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D015232:Dinoprostone / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D009093:Mucus / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; C071423:capsazepine; D002211:Capsaicin; D001920:Bradykinin