Gastro-protective action of lafutidine mediated by capsaicinsensitive afferent neurons without interaction with TRPV1 and involvement of endogenous prostaglandins
AIM： Lafutidine, a histamine H2 receptor antagonist, exhibits gastro-protective action mediated by capsaicinsensitive afferent neurons （CSN）. We compared the effect between lafutidine and capsaicin, with respect to the interaction with endogenous prostaglandins （PG）, nitric oxide （NO） and the affere...
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| Published in: | World journal of gastroenterology : WJG Vol. 12; no. 19; pp. 3031 - 3037 |
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| Main Author: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2006
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | AIM： Lafutidine, a histamine H2 receptor antagonist, exhibits gastro-protective action mediated by capsaicinsensitive afferent neurons （CSN）. We compared the effect between lafutidine and capsaicin, with respect to the interaction with endogenous prostaglandins （PG）, nitric oxide （NO） and the afferent neurons, including transient receptor potential vanilloid subtype 1 （TRPV1）.
METHODS： Male SD rats and C57BL/6 mice, both wildtype and prostacyclin IP receptor knockout animals, were used after 18 h of fasting. Gastric lesions were induced by the po administration of HCl/ethanol （60% in 150 mmol/L HCl） in a volume of 1 mL for rats or 0.3 mL for mice.
RESULTS： Both lafutidine and capsaicin （1-10 mg/kg, po） afforded dose-dependent protection against HCI/ ethanol in rats and mice. The effects were attenuated by both the ablation of CSN and pretreatment with NG-nitro- L-arginine methyl ester, yet only the effect of capsaicin was mitigated by prior administration of capsazepine, the TRPV1 antagonist, as well as indomethacin. Lafutidine protected the stomach against HCl/ethanol in IP receptor knockout mice, similar to wild-type animals, while capsaicin failed to afford protection in the animals lacking IP receptors. Neither of these agents affected the mucosal PGE2 or 6-keto PGF1α contents in rat stomachs. Capsaicin evoked an increase in [Ca^2＋]i in rat TRPV1-transfected HEK293 cells while lafutidine did not.
CONCLUSION： These results suggest that although both lafutidine and capsaicin exhibit gastro-protective action mediated by CSN, the mode of their effects differs regarding the dependency on endogenous PGs/IP receptors and TRPV1. It is assumed that lafutidine interacts with CSN at yet unidentified sites other than TRPV1. |
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| Bibliography: | Lafutidine Prostaglandin Capsaicin-sensirive afferent neuron 14-1219/R A histamine H2-receptor antagonist TRPVt R573 Lafutidine; A histamine H2-receptor antagonist; Gastric protection; Prostaglandin; Capsaicin-sensirive afferent neuron; TRPVt Gastric protection |
| ISSN: | 1007-9327 2219-2840 |