Reactive oxygen species (H(2)O(2)): effects on the gallbladder muscle of guinea pigs.
Reactive oxygen species (ROS) have been implicated in the pathogenesis of muscle dysfunction in acute inflammatory processes. The aim of these studies was to determine the effects of ROS on gallbladder muscle function in vitro. Single muscle cells were obtained by enzymatic digestion. H(2)O(2) (70 microM) caused maximal contraction of up to 14% and blocked the response to CCK-8, ACh, and KCl. It did not affect the contractions induced by guanosine 5'-O-(3-thiotriphosphate), diacylglycerol, and inositol 1,4,5-trisphosphate that circumvent membrane receptors. The contraction induced by H(2)O(2) was inhibited by AACOCF(3) [cytosolic phospholipase A(2) (cPLA(2)) inhibitor], indomethacin (cyclooxygenase inhibitor), chelerythrine [protein kinase C (PKC) inhibitor], or PD-98059 [mitogen-activated protein kinase (MAPK) inhibitor]. H(2)O(2) also reduced the CCK receptor binding capacity from 0.36 +/- 0.05 pmol/mg protein (controls) to 0.17 +/- 0.03 pmol/mg protein. The level of lipid peroxidation as well as the PGE(2) content was significantly increased after H(2)O(2) pretreatment. Unlike superoxide dismutase, the free radical scavenger catalase prevented the H(2)O(2) induced contraction, and its inhibition of the CCK-8 induced contraction. It is concluded that ROS cause damage to the plasma membrane of the gallbladder muscle and contraction through the generation of PGE(2) induced by cPLA(2)-cyclooxygenase and probably mediated by the PKC-MAPK pathway.
Xiao
Zuo-Liang
ZL
Department of Medicine, Rhode Island Hospital and Brown University School of Medicine, 593 Eddy Street, Providence, RI 02903, USA.
Andrada
Maria J  Pozo
MJ
Biancani
Piero
P
Behar
Jose
J
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005704:Gallbladder / Q000166:cytology / Q000502:physiology*; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology*; D016877:Oxidants / Q000494:pharmacology*; D010741:Phospholipases A / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012844:Sincalide / Q000494:pharmacology
D016877:Oxidants; D006861:Hydrogen Peroxide; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D015232:Dinoprostone; D012844:Sincalide; D000109:Acetylcholine