کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9244220 | 1209904 | 2005 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibition of Transient Lower Esophageal Sphincter Relaxation and Gastroesophageal Reflux by Metabotropic Glutamate Receptor Ligands
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
NMDAN-methyl-d-aspartatemGluRMPEPGERDMTEPTLESRl-AP42-methyl-6-(phenylethynyl)-pyridine - 2-متیل-6- (فنیلئتینیل) -پیریدینl-(+)-2-amino-4-phosphonobutyric acid - L - (+) - 2-amino-4-phosphonobutyric acidγ-aminobutyric acid - اسید γ-آمینوبوتیریکgastroesophageal reflux disease - بیماری ریفلاکس معده به مریtransient lower esophageal sphincter relaxation - ترشح اسفنکتر مری ماندگارGABA - گاباMetabotropic glutamate receptor - گیرنده گلوتامات متابوتروپیک
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Background & Aims: Transient lower esophageal sphincter relaxation (TLESR) is the major mechanism of gastroesophageal acid reflux. TLESR is mediated via vagal pathways, which may be modulated by metabotropic glutamate receptors (mGluRs). Group I mGluRs (mGluR1 and 5) have excitatory effects on neurons, whereas group II (mGluR2 and 3) and group III (mGluR4, 6, 7, and 8) are inhibitory. This study determined the effect of mGluRs on triggering of TLESR and reflux in an established conscious ferret model. Methods: Esophageal manometric/pH studies were performed in ferrets with chronic esophagostomies. TLESR were induced by a gastric load of 25 mL glucose (pH 3.5) and 30 mL air. Results: In control treated animals, gastric load induced 3.52 ± 0.46 TLESRs per 47-minute study, 89.7% of which were associated with reflux episodes (n = 16). The mGluR5 antagonist MPEP inhibited TLESR dose dependently, with maximal 71% ± 7% inhibition at 35 μmol/kg (n = 9; P < .0001). MPEP also significantly reduced reflux episodes (P < .001) and increased basal lower esophageal sphincter pressure (P < .05). MPEP inhibited swallowing dose dependently, suggesting a common action on trigger mechanisms for swallowing and TLESR. The more selective analogue, MTEP, had more potent effects (90% ± 6% inhibition TLESR at 40 μmol/kg; n = 8; P < .0001). In contrast, the group I agonist DHPG tended to increase TLESR. The group II agonist (2R, 4R)-APDC was ineffective, whereas the group III agonist L-(AP4 slightly reduced TLESR (33% at 11 μmol/kg; P < .05). The selective mGluR8 agonist (S)-3, 4-DCPG inhibited TLESR by 54% at 15 μmol/kg (P < .01). Conclusions: mGluR5 antagonists potently inhibit TLESR and reflux in ferrets, implicating mGluR5 in the mechanism of TLESR. mGluR5 antagonists are therefore promising as therapy for patients with GERD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 129, Issue 3, September 2005, Pages 995-1004
Journal: Gastroenterology - Volume 129, Issue 3, September 2005, Pages 995-1004
نویسندگان
Claudine L. Frisby, Jan P. Mattsson, Jörgen M. Jensen, Anders Lehmann, John Dent, L. Ashley Blackshaw,