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Effect of Hydrogen Peroxide on VIP-Induced Relaxation of the Cat Lower Esophageal Sphincter
김성효,염지현,이동규,박선영,신창일,류정수,라오현,송현주,민영실,손유동 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.11
We investigated the effects of hydrogen peroxide (H2O2) on relaxation of the cat lower esophageal sphincter (LES). Vasoactive intestinal peptide (VIP) caused dose-dependent relaxation of LES, and H2O2 reduced VIP-induced relaxation. Relaxation was also attenuated by pertussis toxin (PTX), indicating a Gi/o component. VIP treatment increased [35S]GTPγS binding to Gs and Gi3 protein, but not to Go, Gq, Gi1 or Gi2. This increase in Gs or Gi3 binding was reduced by H2O2. However, the relaxation induced by sodium nitroprusside (SNP), 3-morpholino sydnomine (SIN-1), 8-br cGMP (cGMP analog), forskolin (adenylate cyclase activator), and dibutyryl-cAMP (a stable cAMP analog) was not reduced by H2O2. These data suggest that H2O2 inhibits VIP-induced relaxation via a Gi-dependent pathway, perhaps by inhibiting the activation of Gi3 or Gs downstream of the VIP receptor and independent of cAMP or NO-cGMP signaling.