Protective Effect of Lafutidine, a Novel H2-Receptor Antagonist, on Reflux Esophagitis in Rats Through Capsaicin-Sensitive Afferent Neurons
ABSTRACT: We examined the effect of lafutidine, a novel histamine H2-receptor antagonist, on acid reflux esophagitis in rats in relation to capsaicin-sensitive afferent neurons. The esophagitis was induced in rats by ligating both the pylorus and forestomach for 4 h. Lafutidine (1 – 30 mg/kg) and ci...
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Elsevier
2003-01-01
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Series: | Journal of Pharmacological Sciences |
Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319326155 |
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author | Kenji Nagahama Masanori Yamato Shinichi Kato Koji Takeuchi |
author_facet | Kenji Nagahama Masanori Yamato Shinichi Kato Koji Takeuchi |
author_sort | Kenji Nagahama |
collection | DOAJ |
description | ABSTRACT: We examined the effect of lafutidine, a novel histamine H2-receptor antagonist, on acid reflux esophagitis in rats in relation to capsaicin-sensitive afferent neurons. The esophagitis was induced in rats by ligating both the pylorus and forestomach for 4 h. Lafutidine (1 – 30 mg/kg) and cimetidine (100 mg/kg) were administered either intragastrically or intraduodenally, while capsaicin (1 – 30 mg/kg) was administered intragastrically after the dual ligation. Intragastrical administered lafutidine at >3 mg/kg significantly prevented the hemorrhagic esophageal damage induced by the dual ligation, and this effect was mimicked by neither capsaicin nor cimetidine given intragastrically, but totally abolished by sensory deafferentation. In contrast, lafutidine and cimetidine given intraduodenally were both protective against the esophageal damage in a sensory deafferentation-resistant manner. The acid secretion in pylorus-ligated stomachs was significantly inhibited by these agents given intraduodenally, but not intragastrically. Vanilloid receptor subtype 1 (VR1) was expressed abundantly in the stomach, but very weakly expressed in the esophagus as assessed by Western blotting. These results suggest that lafutidine is effective against the esophageal lesions induced by acid reflux through inhibition of acid secretion and capsaicin-sensitive afferent neurons. The latter mechanism, not shared by cimetidine, may be due to the interaction of lafutidine with unidentified sites on sensory neurons other than VR1. |
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spelling | doaj.art-d0d02659bb38437dbe15032a6e0a1ad52022-12-22T03:18:48ZengElsevierJournal of Pharmacological Sciences1347-86132003-01-019315561Protective Effect of Lafutidine, a Novel H2-Receptor Antagonist, on Reflux Esophagitis in Rats Through Capsaicin-Sensitive Afferent NeuronsKenji Nagahama0Masanori Yamato1Shinichi Kato2Koji Takeuchi3Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, JapanDepartment of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, JapanDepartment of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, JapanDepartment of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, JapanABSTRACT: We examined the effect of lafutidine, a novel histamine H2-receptor antagonist, on acid reflux esophagitis in rats in relation to capsaicin-sensitive afferent neurons. The esophagitis was induced in rats by ligating both the pylorus and forestomach for 4 h. Lafutidine (1 – 30 mg/kg) and cimetidine (100 mg/kg) were administered either intragastrically or intraduodenally, while capsaicin (1 – 30 mg/kg) was administered intragastrically after the dual ligation. Intragastrical administered lafutidine at >3 mg/kg significantly prevented the hemorrhagic esophageal damage induced by the dual ligation, and this effect was mimicked by neither capsaicin nor cimetidine given intragastrically, but totally abolished by sensory deafferentation. In contrast, lafutidine and cimetidine given intraduodenally were both protective against the esophageal damage in a sensory deafferentation-resistant manner. The acid secretion in pylorus-ligated stomachs was significantly inhibited by these agents given intraduodenally, but not intragastrically. Vanilloid receptor subtype 1 (VR1) was expressed abundantly in the stomach, but very weakly expressed in the esophagus as assessed by Western blotting. These results suggest that lafutidine is effective against the esophageal lesions induced by acid reflux through inhibition of acid secretion and capsaicin-sensitive afferent neurons. The latter mechanism, not shared by cimetidine, may be due to the interaction of lafutidine with unidentified sites on sensory neurons other than VR1.http://www.sciencedirect.com/science/article/pii/S1347861319326155 |
spellingShingle | Kenji Nagahama Masanori Yamato Shinichi Kato Koji Takeuchi Protective Effect of Lafutidine, a Novel H2-Receptor Antagonist, on Reflux Esophagitis in Rats Through Capsaicin-Sensitive Afferent Neurons Journal of Pharmacological Sciences |
title | Protective Effect of Lafutidine, a Novel H2-Receptor Antagonist, on Reflux Esophagitis in Rats Through Capsaicin-Sensitive Afferent Neurons |
title_full | Protective Effect of Lafutidine, a Novel H2-Receptor Antagonist, on Reflux Esophagitis in Rats Through Capsaicin-Sensitive Afferent Neurons |
title_fullStr | Protective Effect of Lafutidine, a Novel H2-Receptor Antagonist, on Reflux Esophagitis in Rats Through Capsaicin-Sensitive Afferent Neurons |
title_full_unstemmed | Protective Effect of Lafutidine, a Novel H2-Receptor Antagonist, on Reflux Esophagitis in Rats Through Capsaicin-Sensitive Afferent Neurons |
title_short | Protective Effect of Lafutidine, a Novel H2-Receptor Antagonist, on Reflux Esophagitis in Rats Through Capsaicin-Sensitive Afferent Neurons |
title_sort | protective effect of lafutidine a novel h2 receptor antagonist on reflux esophagitis in rats through capsaicin sensitive afferent neurons |
url | http://www.sciencedirect.com/science/article/pii/S1347861319326155 |
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