Mechanism of action of intracisternal apolipoprotein A-IV in inhibiting gastric acid secretion in rats

Gastroenterology. 1995 Nov;109(5):1583-8. doi: 10.1016/0016-5085(95)90647-9.

Abstract

Background & aims: We recently showed that intracisternal injection of apolipoprotein A-IV (apo A-IV), a protein produced by the small intestine in response to fat, inhibits gastric acid secretion. The aim of this study was to investigate the mechanism of acid inhibition by central apo A-IV.

Methods: Gastric acid secretion was determined in pylorus-ligated conscious rats. The effect of intracisternal injection of apo A-IV on gastric acid secretion stimulated by pentagastrin, bethanechol, or intracisternal thyrotropin-releasing hormone (central vagal stimulant) was examined. The effects of vagotomy, indomethacin, and adrenergic blockers on the acid inhibition of apo A-IV were examined to investigate the role of the vagal system, prostaglandin pathways, and adrenergic system.

Results: Intracisternal apo A-IV significantly inhibited pentagastrin-, bethanechol-, and thyrotropin-releasing hormone-stimulated gastric acid secretion in a similar fashion. Inhibition of pentagastrin-stimulated acid secretion by apo A-IV still occurred even in vagotomized rats. Yohimbine but not indomethacin or propranolol eliminated apo A-IV--induced inhibition of acid.

Conclusions: Intracisternal apo A-IV inhibits gastric acid secretion through alpha 2-adrenergic receptors. The vagal pathway and the prostaglandin system are not involved in apo A-IV--induced acid inhibition.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Apolipoproteins A / administration & dosage
  • Apolipoproteins A / pharmacology*
  • Bethanechol / pharmacology
  • Brain / drug effects
  • Depression, Chemical
  • Gastric Acid / metabolism*
  • Indomethacin / pharmacology
  • Male
  • Pentagastrin / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Thyrotropin-Releasing Hormone / pharmacology
  • Vagotomy

Substances

  • Adrenergic beta-Antagonists
  • Apolipoproteins A
  • apolipoprotein A-IV
  • Bethanechol
  • Thyrotropin-Releasing Hormone
  • Pentagastrin
  • Indomethacin