Effect of orogastric nicotine on rat gastric mucosal gel thickness, surface cell viability and intracellular pH.
Intracellular pH was measured in vivo using a fluorescent, microscopic technique in gastric surface cells of rats exposed to orogastric nicotine on an acute or chronic basis. Mucosae were superfused with solutions of pH 3 or pH 1.7 in order to examine the rate of intracellular acidification and recovery. In rats acutely exposed to nicotine, the response of intracellular pH to superfusion with acidic solutions was blunted with respect to control rats in a dose-dependent manner. In contrast, intracellular pH of rats chronically treated with nicotine had an exaggerated response with respect to control rats, with more rapid acidification and diminished ability to maintain intracellular pH in the physiologic range. Mucus gel thickness was increased after acute nicotine exposure in a dose-dependent manner, whereas a dose-dependent decrease in thickness was seen after chronic nicotine exposure. Cell viability using the fluorescent vital dye propidium iodide was increased in rats acutely treated with orogastric nicotine; conversely, viability was decreased in chronically treated rats. We conclude that acute nicotine exposure diminishes, whereas chronic nicotine exposure enhances, the effect of luminal acidity on mucosal surface cell intracellular pH and cell viability. These divergent effects correlate inversely with mucus gel thickness, suggesting that the mucus gel layer is an important component of the gastric mucosal barrier.
Wadsworth Veterans Affairs Medical Center, Department of Medicine, University of California, Los Angeles.
J D
JD
Kaunitz
Y
Y
Nishizaki
K
K
Kaneko
P H
PH
Guth
D000284:Administration, Oral; D000818:Animals; D002021:Buffers; D002470:Cell Survival / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006863:Hydrogen-Ion Concentration; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002021:Buffers; D009538:Nicotine