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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA007255-02
Application #
3110979
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1987-04-01
Project End
1990-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Loyola University Chicago
Department
Type
Schools of Medicine
DUNS #
791277940
City
Maywood
State
IL
Country
United States
Zip Code
60153
Keshavarzian, A; Holmes, E W; Patel, M et al. (1999) Leaky gut in alcoholic cirrhosis: a possible mechanism for alcohol-induced liver damage. Am J Gastroenterol 94:200-7
Ashrani, A; Keshavarzian, A; Jacyno, M et al. (1997) Are dipyridamole (sensitive) calcium channels present in esophageal smooth muscle? Life Sci 60:PL423-30
Keshavarzian, A; Muska, B; Sundaresan, R et al. (1996) Ethanol at pharmacologically relevant concentrations inhibits contractility of isolated smooth muscle cells of cat esophagus. Alcohol Clin Exp Res 20:180-4
Fields, J Z; Jacyno, M; Wasyliw, R et al. (1995) Ethanol inhibits contractility of esophageal smooth muscle strips. Alcohol Clin Exp Res 19:1403-13
Keshavarzian, A; Zorub, O; Sayeed, M et al. (1994) Acute ethanol inhibits calcium influxes into esophageal smooth but not striated muscle: a possible mechanism for ethanol-induced inhibition of esophageal contractility. J Pharmacol Exp Ther 270:1057-62
Keshavarzian, A; Fields, J Z; Vaeth, J et al. (1994) The differing effects of acute and chronic alcohol on gastric and intestinal permeability. Am J Gastroenterol 89:2205-11
Fields, J Z; Turk, A; Durkin, M et al. (1994) Increased gastrointestinal symptoms in chronic alcoholics. Am J Gastroenterol 89:382-6
Keshavarzian, A; Polepalle, C; Iber, F L et al. (1992) Secondary esophageal contractions are abnormal in chronic alcoholics. Dig Dis Sci 37:517-22
Keshavarzian, A; Gordon, J H; Willson, C et al. (1992) Chronic ethanol feeding produces a muscarinic receptor upregulation, but not a muscarinic supersensitivity in lower esophageal sphincter muscle. J Pharmacol Exp Ther 260:601-7
Keshavarzian, A; Urban, G; Sedghi, S et al. (1991) Effect of acute ethanol on esophageal motility in cat. Alcohol Clin Exp Res 15:116-21

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