Reversible esophageal motor changes have been identified in chronically alcoholic men, including elevated lower esophageal sphincter pressure and increased contraction amplitude in the body of the esophagus. Acute alcohol use, on the other hand, caused diminution of the pressure in both sites inb man. The hypothesis to be investigated is that diminished neurohumoral transmitter release accounts for the decreased pressure from the acute alcohol exposure; in contrast, increased receptor sensitivity to neurotransmitters in the esophageal muscle accounts for the increased pressures that follow chronic alcohol exposure. To this end, separate groups of cats are to be studied during (1) acute infusion of alcohol, or (2) after several weeks of alcohol ingestion, or (3) during the withdrawal phase soon after the termination of chronic use. Esophageal motor function will be studied following acute paranteral administration of bethanechol, atropine, phenylephrine, phentolamine, pentagastrin, Substance P or bombesin to determine whether cholinergic, adrenergic and/or peptidergic neurotransmitter systems are involved in the effects of alcohol in the manner predicted by the hypothesis. In addition, the physiological effects of vagotomy, and tetrodotoxin administration will suggest whether changes in presynaptic neural functions are involved in the effects of alcohol. In man, normal and chronic alcoholic subjects are to be studied for esophageal motility changes during alcohol infusion and during the administration of bethanechol, atropine, and pentagastrin. These studies are expected to indicate the more important neurochemical mediators of the acute and chronic alcohol-related esophageal motor changes and suggest methods of treating them. The increased incidence of esophageal cancer and esophagitis in the alcoholic may be related to these changes.
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