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Am J Physiol Gastrointest Liver Physiol (September 27, 2007). doi:10.1152/ajpgi.00206.2007
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Submitted on May 7, 2007
Accepted on September 19, 2007

Reactive oxygen species [ROS] are messengers in maintenance of human and guinea pig gallbladder tonic contraction

Ping Cong1, Zuo-Liang Xiao1, Piero Biancani2, and Jose Behar3*

1 GI Motility Research Laboratory, Rhode Island Hospital, Providence, Rhode Island, United States
2 Medicine, Brown University, Providence, , Rhode Island, United States; GI Motility Research Laboratory, Rhode Island Hospital, Providence, Rhode Island, United States
3 Medicine, Brown University, Providence, Rhode Island, United States; GI Motility Research Laboratory, Rhode Island Hospital, Providence, Rhode Island, United States

* To whom correspondence should be addressed. E-mail: jose_behar{at}brown.edu.

Background: The tonic contraction of human and guinea pig gallbladder (GB) is dependent on basal levels of PGE2 and TXA2. The pathway involved in the genesis of these prostaglandins has not been elucidated. Aims: to examine the source of Reactive Oxygen Species (ROS) and whether they contribute to the genesis of GB tonic contraction by generating basal prostaglandin levels. Methods: Tonic contraction was studied in human and guinea pig GB muscle strips treated with ROS scavengers (tiron and catalase), apocynin (an inhibitor of NADPH oxidase) and NOX-1 siRNA. The subunits of NADPH oxidase and their functional roles were determined with specific antibodies in GB muscle cells. Results: ROS scavengers reduced the GB tonic contraction and H2O2 and PGE2 levels. Apocynin also inhibited the tonic contraction. Antibodies against subunits of NADPH oxidase present in GB muscle cells lowered H2O2 and PGE2 levels. NOX-1 siRNA transfection reduced the tonic contraction, NOX-1 expression, and levels of H2O2 and PGE2. Tiron and apocynin inhibited the expected increase in tension and H2O2 levels induced by stretching of muscle strips. H2O2 increased the levels of PGE2 and TXA2 by increasing PAF-like lipids that phosphorylates p38 and cPLA2 sequentially. Conclusion: H2O2 generated by NADPH oxidase participates in a signal transduction pathway that maintains the GB tonic contraction by activating PAF, p38, and cPLA2 to generate prostaglandins.






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