A cerebral nitrergic pathway modulates endotoxin-induced changes in gastric motility.
1. This study analyses the neural pathway involved in the modulation of gastric motor function by stress. 2. Systemic administration of low doses of endotoxin (40 microg kg(-1), i.v.) prevents the increase in gastric tone induced by 2-deoxy-D-glucose (200 mg kg(-1), i.v., 2-DG) in urethane-anaesthetized rats. 3. Functional inhibition of afferent neurones by systemic administration of capsaicin (20+30+50 mg kg(-1), i.m.) in adult rats prevented the inhibitory effects of endotoxin. 4. Pre-treatment with the nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), both i.v. (10 mg kg(-1)) and i.c. (200 microg rat(-1)), prevented the inhibitory effects of endotoxin on gastric tone induced by 2-DG. 5. Immunohistochemical studies show Fos expression in the dorsal vagal complex (DVC) of the brainstem of 2-DG-treated animals. Peripheral administration of endotoxin (40 microg kg(-1), i.p.) increased the number of Fos-immunoreactive cells induced by 2-DG, both in the nucleus tractus solitarii (NTS) and in the dorsal motor nucleus (DMN) of the DVC. Pre-treatment with L-NAME prevented the increase in Fos expression induced by endotoxin in both nuclei. 6. Endotoxin (40 microg kg(-1), i.p.) increased Ca(2+)-dependent nitric oxide synthase (cNOS) activity in the brainstem. Addition of 7-nitroindazole (600 microM, 7-NI) to the assay significantly inhibited the increase in cNOS activity caused by endotoxin. No change in NOS activity of any isoform was observed in the stomach of animals treated with endotoxin. 7. The present study suggests that inhibition of gastric motor function by low doses of endotoxin involves activation of capsaicin-sensitive afferent neurones and neuronal NOS in the brainstem.
Quintana
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Department of Pharmacology, Faculty of Medicine, University of Valencia, Avd. Blasco Ibáñez 15, 46010 Valencia, Spain.
García-Zaragozá
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Martínez-Cuesta
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Calatayud
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Esplugues
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JV
Barrachina
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MD
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D001933:Brain Stem / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011312:Pressure; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013270:Stomach / Q000187:drug effects / Q000502:physiology
D004731:Endotoxins; D004791:Enzyme Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D003847:Deoxyglucose; D019001:Nitric Oxide Synthase; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester