The existence of an NAD-dependent pathway for retinoic acid formation from vitamin A (retinol) in rat esophagus and its inhibition by ethanol and histamine 2 (H₂) receptor antagonists

Background: Retinoic acid is essential for normal cell differentiation and proliferation and disturbance of its metabolism has been implicated in the pathogenesis of various disorders including malignancy. Retinoic acid has been demonstrated to be produced from retinol via a two step oxidation pathway in which alcohol dehydrogenase isozymes have roles. The aim of this study was to know whether the rat esophagus would have the pathway and whether the retinoic acid formation could be disturbed when alcohol dehydrogenase was hampered. Material/Methods: Rat esophageal cytosolic fraction, nicotinamide adenine dinucleotide, and all-trans retinol were incubated together and produced all-trans retinoic acid was detected by high performance liquid chromatography method. Results: Remarkable all-trans retinoic acid formation was observed only when nicotinamide adenine dinucleotide was in existence. The all-trans retinoic acid formation was hampered by addition of ethanol, another substrate of alcohol dehydrogenase, and some histamine 2 receptor antagonists, inhibitors of alcohol dehydrogenase. Conclusions: These results suggest that rat esophagus has an nicotinamide adenine dinucleotide-dependent all-trans retinoic acid formation pathway in which alcohol dehydrogenase is involved. We hypothesize that disturbance of the all-trans retinoic acid formation pathway by ethanol and histamine 2 receptors may cause various esophageal disorders including esophageal cancer seen in alcoholics and subjects taking histamine 2 receptors excessively.