Apolipoprotein A-IV stimulates duodenal vagal afferent activity to inhibit gastric motility via a CCK1 pathway.
Apolipoprotein A-IV (apo A-IV), a peptide expressed by enterocytes in the mammalian small intestine and released in response to long-chain triglyceride absorption, may be involved in the regulation of gastric acid secretion and gastric motility. The specific aim of the present study was to determine the pathway involved in mediating inhibition of gastric motility produced by apo A-IV. Gastric motility was measured manometrically in response to injections of either recombinant purified apo A-IV (200 microg) or apo A-I, the structurally similar intestinal apolipoprotein not regulated by triglyceride absorption, close to the upper gastrointestinal tract in urethane-anesthetized rats. Injection of apo A-IV significantly inhibited gastric motility compared with apo A-I or vehicle injections. The response to exogenous apo A-IV injections was significantly reduced by 77 and 55%, respectively, in rats treated with the CCK(1) receptor blocker devazepide or after functional vagal deafferentation by perineural capsaicin treatment. In electrophysiological experiments, isolated proximal duodenal vagal afferent fibers were recorded in vitro in response to close-arterial injection of vehicle, apo A-IV (200 microg), or CCK (10 pmol). Apo A-IV stimulated the discharge of duodenal vagal afferent fibers, significantly increasing the discharge in 4/7 CCK-responsive units, and the response was abolished by CCK(1) receptor blockade with devazepide. These data suggest that apo A-IV released from the intestinal mucosa during lipid absorption stimulates the release of endogenous CCK that activates CCK(1) receptors on vagal afferent nerve terminals initiating feedback inhibition of gastric motility.
Glatzle
J
J
Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis 95616, USA.
Darcel
N
N
Rechs
A J
AJ
Kalogeris
T J
TJ
Tso
P
P
Raybould
H E
HE
D000818:Animals; D001054:Apolipoproteins A / Q000494:pharmacology* / Q000502:physiology; D002766:Cholecystokinin / Q000494:pharmacology; D003714:Denervation; D020109:Devazepide / Q000494:pharmacology; D004386:Duodenum / Q000294:innervation* / Q000502:physiology; D005746:Gastric Emptying / Q000502:physiology*; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A / Q000378:metabolism*; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology; D017833:Visceral Afferents / Q000187:drug effects / Q000502:physiology
D001054:Apolipoproteins A; D006727:Hormone Antagonists; D043886:Receptor, Cholecystokinin A; C022205:apolipoprotein A-IV; D002766:Cholecystokinin; D020109:Devazepide