Lysolecithin-lipid interactions in disruption of the canine gastric mucosal barrier.
Lysolecithin has been implicated in the pathogenesis of gastric ulcer and reflux gastritis. By use of canine Heidenhain pouches, we examined effects of lysolecithin on the gastric mucosal barrier both at neutral (PO4 buffer, pH 7) and acidic (0.15 M HCl) pH with respect to interaction of lysolecithin with membrane lipids. At both pH values, 2 mM lysolecithin significantly increased forward diffusion of Na+ and backdiffusion of H+. Both solutions also caused significant efflux of membrane phospholipid and cholesterol. Saturation of neutral and acidic lysolecithin solutions with either lecithin or cholesterol significantly diminished or completely prevented disruption of the barrier to H+ backdiffusion and Na+ forward diffusion. In agreement with other reports, we also demonstrated formation of soluble lysolecithin-lecithin mixed micelles but formation of insoluble lysolecithin-cholesterol complexes. Finally, by use of [3H]polyethylene glycol and [14C]lysolecithin, we demonstrated more rapid mucosal uptake of lysolecithin at acidic than at neutral pH for any given experimental condition. Specifically, mean mucosal uptake of lysolecithin from acidic solutions saturated with lecithin (which did not disrupt the gastric mucosal barrier) was greater than uptake from neutral solutions without added lipid (which did disrupt the barrier). These studies suggest that lysolecithin-lipid interactions play an important role in lysolecithin-induced injury to the gastric mucosa. The most important of these interactions appears to occur in luminal lysolecithin micelles rather than within mucosal membranes.
Duane
W C
WC
McHale
A P
AP
Sievert
C E
CE
D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D004285:Dogs; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000378:metabolism* / Q000494:pharmacology; D008563:Membrane Lipids / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D013270:Stomach / Q000502:physiology
D007473:Ion Channels; D008244:Lysophosphatidylcholines; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010743:Phospholipids; D002784:Cholesterol