Apelin stimulation of duodenal bicarbonate secretion: feeding-dependent and mediated via apelin-induced release of enteric cholecystokinin.
OBJECTIVE
Apelin peptides are the endogenous ligand of the G protein-coupled receptor APJ. Proposed actions include involvement in control of cardiovascular functions, appetite and body metabolism. We have investigated the effects of apelin peptides on duodenal bicarbonate secretion in vivo and the release of cholecystokinin (CCK) from acutely isolated mucosal cells and the neuroendocrine cell line STC-1.


METHODS
Lewis × Dark Agouti rats had free access to water and, unless fasted overnight, free access to food. A segment of proximal duodenum was cannulated in situ in anaesthetized animals. Mucosal bicarbonate secretion was titrated (pH stat) and apelin was administered to the duodenum by close intra-arterial infusion. Total RNA was extracted from mucosal specimens, reverse transcripted to cDNA and the expression of the APJ receptor measured by quantitative real-time PCR. Apelin-induced release of CCK was measured using (1) cells prepared from proximal small intestine and (2) STC-1 cells.


RESULTS
Even the lowest dose of apelin-13 (6 pmol kg⁻¹ h⁻¹) caused a significant rise in bicarbonate secretion. Stimulation occurred only in continuously fed animals and even a 100-fold greater dose (600 pmol kg⁻¹ h⁻¹) of apelin was without effect in overnight food-deprived animals. Fasting also induced an eightfold decrease in the expression of APJ receptor mRNA. Apelin induced significant release of CCK from both mucosal and STC-1 cells, and the CCK(A) receptor antagonist devazepide abolished bicarbonate secretory responses to apelin.


CONCLUSIONS
Apelin-induced stimulation of duodenal electrolyte secretion is feeding-dependent and mediated by local mucosal release of CCK.
Flemström
G
G
Department of Neuroscience, Uppsala University, Sweden. gunnar.flemstrom@neuro.uu.se
Mäkelä
K
K
Purhonen
A K
AK
Sjöblom
M
M
Jedstedt
G
G
Walkowiak
J
J
Herzig
K H
KH
D000818:Animals; D000075244:Apelin Receptors; D001285:Atropine / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D002460:Cell Line; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020109:Devazepide / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism*; D004435:Eating; D005508:Food Deprivation / Q000502:physiology; D006801:Humans; D007261:Infusions, Intra-Arterial; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D014363:Tryptamines / Q000494:pharmacology
D000075244:Apelin Receptors; C491284:Aplnr protein, rat; D001639:Bicarbonates; D036341:Intercellular Signaling Peptides and Proteins; D010276:Parasympatholytics; D043562:Receptors, G-Protein-Coupled; D014363:Tryptamines; C495199:apelin-13 peptide; C057154:luzindole; D001285:Atropine; D002766:Cholecystokinin; D020109:Devazepide; D015232:Dinoprostone