[A cytoprotective chloride channel in gastric parietal cells].
This review summarizes the regulatory mechanisms and physiological functions of the novel sub-pS Cl- channel (0.3 pS) that is present abundantly in the basolateral membrane of rabbit gastric parietal cells. The sub-pS Cl- channel is voltage-independent and inhibited by NPPB, a Cl- channel blocker. We found that this gastric Cl- channel is linked to three important physiological roles. First, the sub-pS Cl- channel has a housekeeping role through dominating the cell membrane potential. Although several types of cation channels are present, they do not significantly contribute to the membrane potential in the parietal cells. Second, the Cl- channel is activated by prostaglandin E2 via the EP3 receptor/Ca2-/nitric oxide (NO)/cGMP pathway. A vasodilator ecabapide also activates the channel by increasing the intracellular cGMP content. The NO/cGMP pathway-mediated opening of the sub-pS Cl- channel is essential for cytoprotection against ethanol-induced damage in the gastric parietal cells. The NO/cGMP-elicited cytoprotection is abolished by NPPB. To our knowledge, this Cl- channel is the first identified target for the cytoprotective NO/cGMP pathway. Third, the sub-pS Cl- channel is inhibited by the GTP-binding protein-mediated intracellular production of superoxide anion. Hydrogen peroxide and hydroxyl radicals have no effect on the channel activity. The intracellular superoxide anion acts as a messenger in the negative regulatory mechanism of the sub-pS Cl- channel. The similar sub-pS Cl- channel is also found in rat gastric parietal cells.
Sakai
H
H
Department of Pharmaceutical Physiology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
D000818:Animals; D018118:Chloride Channels / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology; D019610:Cytoprotection; D015232:Dinoprostone / Q000502:physiology; D008564:Membrane Potentials; D009569:Nitric Oxide / Q000502:physiology; D010295:Parietal Cells, Gastric / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017382:Reactive Oxygen Species / Q000502:physiology
D018118:Chloride Channels; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D006152:Cyclic GMP; D015232:Dinoprostone