Reduction of asymmetric dimethylarginine in the protective effects of rutaecarpine on gastric mucosal injury.
Our recent study has shown that asymmetric dimethylarginine (ADMA) plays an important role in facilitating gastric mucosal injury by multiple factors. To explore whether the protection of rutaecarpine against gastric mucosal injury is related to reduction of ADMA content, a model of ethanol-induced gastric mucosal injury in rats was selected for this study. The ulcer index, the content of ADMA and NO, and the activity of dimethylarginine dimethylaminohydrolase (DDAH) in gastric tissues were measured in vivo after pretreatment with rutaecarpine. The in vitro effect of rutaecarpine on the release of calcitonin gene-related peptide (CGRP) and NO from isolated gastric tissues was also determined. The results showed that ethanol significantly increased the ulcer index, decreased the DDAH activity and the NO level, and elevated the ADMA level, which was attenuated by pretreatment with rutaecarpine (0.6 mg/kg or 1.2 mg/kg). In the isolated gastric tissues, rutaecarpine significantly increased the release of both CGRP and NO; the release of NO, but not CGRP, was abolished in the presence of l-NAME (10(-4) mol/L). The present results suggest that rutaecarpine protects the gastric mucosa against injury induced by ethanol and that the gastroprotection of rutaecarpine is related to reduction of ADMA levels through stimulating the release of CGRP.
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, No.110 Xiang-Ya Road, Changsha 410078, China.
Ying-Zi
YZ
Liu
Yuan
Y
Zhou
Dai
D
Li
Li
L
Wang
Gao-Yun
GY
Hu
Jun
J
Peng
Yuan-Jian
YJ
Li
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D000897:Anti-Ulcer Agents; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol; D005753:Gastric Mucosa / Q000473:pathology*; D007202:Indicators and Reagents; D026121:Indole Alkaloids / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D020011:Protective Agents; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D052999:Quinazolinones
D000581:Amidohydrolases; D000897:Anti-Ulcer Agents; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide; D004791:Enzyme Inhibitors; D000431:Ethanol; D007202:Indicators and Reagents; D026121:Indole Alkaloids; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D020011:Protective Agents; D011799:Quinazolines; C487735:dimethylarginine; C028632:rutecarpine; D052999:Quinazolinones; C059999:dimethylargininase