Effect of hydrogen peroxide on VIP-induced relaxation of the cat lower esophageal sphincter.
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]GTPgammaS binding to Gs and Gi3 protein, but not to Go, Gq, Gil 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 H202 inhibits VIP-induced relaxation via a Gi-dependent pathway, perhaps by inhibiting the activation of G(i3) or Gs downstream of the VIP receptor and independent of cAMP or NO-cGMP signaling.
Kim
Sung Hyo
SH
Department of Pharmacology, College of Pharmacy, Chung Ang University, Seoul 156-756, Korea.
Youm
Ji Hyun
JH
Lee
Dong Kyu
DK
Park
Sun Young
SY
Shin
Chang Yell
CY
Ryu
Jung Su
JS
La
Hyen O
HO
Song
Hyun Ju
HJ
Min
Young Sil
YS
Sohn
Uy Dong
UD
D000818:Animals; D002415:Cats; D005576:Colforsin / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D049630:Esophageal Sphincter, Lower / Q000187:drug effects* / Q000502:physiology; D005260:Female; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D005576:Colforsin; D014660:Vasoactive Intestinal Peptide; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006861:Hydrogen Peroxide; D006152:Cyclic GMP