RESUMEN
Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder. In the present study, we investigated TRP vanilloid subfamily member 2 (TRPV2) expression in lower oesophageal sphincter (LES) and its involvement in acid reflux oesophagitis in rats. Expression of TRPV2 and nerve growth factor mRNAs was significantly enhanced in LES of rats with reflux oesophagitis compared with normal rats. TRPV2 was mainly expressed in inhibitory motor neurons, and partly in intrinsic and extrinsic primary afferent neurons, and macrophages in LES of normal and reflux oesophagitis rats. Number of TRPV2-immunopositive nerve fibres was significantly increased, but that of nNOS-, CGRP-, and PGP9.5-nerve fibres was not changed in reflux oesophagitis compared with normal group. Probenecid produced nitric oxide production and relaxation in LES and this response was significantly enhanced in oesophagitis compared with normal group. Probenecid-induced relaxant effect was blocked by a TRPV2 inhibitor, tranilast, and a NOS inhibitor, NG-nitro-l-arginine methyl ester, in reflux oesophagitis rats. Oral administration of tranilast significantly improved body weight loss, oesophageal lesions, and epithelial thickness in oesophagitis model. These results suggest that up-regulation of TRPV2 in inhibitory motor neurons is involved in LES relaxation in oesophagitis model. TRPV2 inhibition might be beneficial for treatment of GERD.
Asunto(s)
Esfínter Esofágico Inferior/metabolismo , Reflujo Gastroesofágico/tratamiento farmacológico , Reflujo Gastroesofágico/genética , Expresión Génica/genética , Canales Catiónicos TRPV/genética , Canales Catiónicos TRPV/metabolismo , Animales , Modelos Animales de Enfermedad , Esfínter Esofágico Inferior/efectos de los fármacos , Masculino , Relajación Muscular/efectos de los fármacos , Óxido Nítrico/metabolismo , Probenecid/antagonistas & inhibidores , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Canales Catiónicos TRPV/antagonistas & inhibidores , ortoaminobenzoatos/farmacología , ortoaminobenzoatos/uso terapéuticoRESUMEN
The quartz-crystal microbalance (QCM) technique was applied to investigate the interaction of tea catechins with lipid bilayers. The association constants obtained from the frequency changes of QCM revealed that (-)epicatechin gallate and (-)epigallocatechin gallate interacted with 1,2-dimyristoyl-sn-glycero-3-phosphocholine ca. 1000 times more strongly than (-)epicatechin and (-)epigallocatechin. The results exhibited good correlation with the strength of biological activity.
Asunto(s)
Catequina/análogos & derivados , Catequina/química , Dimiristoilfosfatidilcolina/química , Membrana Dobles de Lípidos/química , Cuarzo/química , Té/química , Adsorción , CinéticaRESUMEN
Spontaneous changes in the morphology of cell-size liposomes (dioleoylphosphatidylcholine, DOPC and egg PC) as model cells were investigated in the presence of cholesterol. Tube structures and liposome networks connected by the tubes were observed in the presence of 5-30% cholesterol by dark-field and laser-scanning microscopy. Furthermore, in the presence of more than 40 mol% of cholesterol, the tubes disappeared and changed to small liposomes. Thus, cholesterol induced a morphological change in giant liposomes from tubes to small liposomes. These phenomena may be related to the role of cholesterol in the morphological changes in living cells such as neurons.