Effects of Dopamine and Alpha-2 Adrenoreceptor Blockade on L-Dopa and Cholecystokinin-Induced Gastroprotection

James M. Cross, David W Mercer, Jeffrey Gunter, Thomas A. Miller

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Dopamine and cholecystokinin have been colocalized in neurons and represent endogenous enteric neurotransmitters. Both peptides possess potent protective actions against gastric injury when given exogenously. This study was undertaken in conscious female rats to test the hypothesis that cholecystokinin may exert its protective actions via release of dopamine. Experiments were designed to ascertain whether L-dopa, a dopamine precursor, could prevent gastric injury with the same degree of efficacy as cholecystokinin and to determine what role alpha-2 adrenoreceptors and dopamine receptors play in mediating the protective actions of these peptides. Intraperitoneal administration of L-dopa (1 to 25 mg/kg) in a dose-dependent manner prevented the type of macroscopic injury to the acid-secreting portion of the stomach that is caused by 1 ml of orogastric acidified ethanol (150 mmol/L hydrochloric acid/50% ethanol), an effect corroborated by histologic examination. Administration of either the alpha-2 adreno-receptor antagonist yohimbine (0.1 to 1.0 mg/kg) or the dopamine receptor antagonist haloperidol (1 to 5 mg/kg) caused a partial reversal of L-dopa-induced protection but not the protective actions of subcutaneous cholecystokinin (100 μg/kg). Simultaneous administration of both receptor antagonists had an additive effect and completely reversed the protective actions of L-dopa. The dopamine precursor L-dopa was just as effective in maintaining the integrity of the gastric epithelium in the face of a damaging insult as the gut peptide cholecystokinin. However, the data indicate that L-dopa initiates its protective actions through activation of both alpha-2 adrenoreceptors and dopamine receptors, whereas the protective effects of cholecystokinin are elicited by means of a different mechanism.

Original languageEnglish (US)
Pages (from-to)257-265
Number of pages9
JournalJournal of Gastrointestinal Surgery
Volume1
Issue number3
DOIs
StatePublished - Jan 1 1997

Fingerprint

Cholecystokinin
Levodopa
Dopamine
Stomach
Dopamine Receptors
Peptides
Wounds and Injuries
Ethanol
Yohimbine
Dopamine Antagonists
Hydrochloric Acid
Haloperidol
Neurotransmitter Agents
Epithelium
Neurons
Acids

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology

Cite this

Effects of Dopamine and Alpha-2 Adrenoreceptor Blockade on L-Dopa and Cholecystokinin-Induced Gastroprotection. / Cross, James M.; Mercer, David W; Gunter, Jeffrey; Miller, Thomas A.

In: Journal of Gastrointestinal Surgery, Vol. 1, No. 3, 01.01.1997, p. 257-265.

Research output: Contribution to journalArticle

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