Mechanism of action of intracisternal apolipoprotein A-IV in inhibiting gastric acid secretion in rats.
OBJECTIVE
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.
Okumura
T
T
Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
Fukagawa
K
K
Tso
P
P
Taylor
I L
IL
Pappas
T N
TN
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001054:Apolipoproteins A / Q000008:administration & dosage / Q000494:pharmacology*; D018723:Bethanechol / Q000494:pharmacology; D001921:Brain / Q000187:drug effects; D003864:Depression, Chemical; D005744:Gastric Acid / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014628:Vagotomy
D000319:Adrenergic beta-Antagonists; D001054:Apolipoproteins A; C022205:apolipoprotein A-IV; D018723:Bethanechol; D013973:Thyrotropin-Releasing Hormone; D010418:Pentagastrin; D007213:Indomethacin