Cholecystokinin but not ghrelin stimulates mucosal bicarbonate secretion in rat duodenum: Independence of feeding status and cholinergic stimuli
2013 (English)In: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 183, 46-53 p.Article in journal (Refereed) Published
Cholecystokinin (CCK) is an important regulator of food digestion but its influence on small intestinal secretion has received little attention. We characterized effects of CCK-8, ghrelin and some related peptides on duodenal HCO3- secretion in vivo and demonstrated CCK-induced calcium signaling in acutely isolated enterocytes. A segment of proximal duodenum with intact blood supply was cannulated in situ in anaesthetized rats. Mucosal HCO3- secretion was continuously recorded (pH-stat). Peptides were administrated to the duodenum by close intra-arterial infusion. Clusters of duodenal enterocytes were attached to the bottom of a perfusion chamber. The intracellular calcium concentration ([Ca2+](i)) was examined by dual-wavelength imaging. CCK-8 (3.0, 15 and 60 pmol/kg,h) caused dose-dependent increases (p < 0.01) in duodenal alkaline secretion in both overnight fasted and continuously fed animals. The CCK1R-antagonist devazepide but neither the CCK2R-antagonist YMM022 nor the melatonin MT2-selective antagonist luzindole inhibited the rise in secretion. Atropine decreased sensitivity to CCK-8. The appetite-related peptide ghrelin was without effect on the duodenal secretion in fasted as well as fed animals. Superfusion with CCK-8 (1.0-50 nM) induced [Ca2+](i) signaling in acutely isolated duodenal enterocytes. After an initial peak response, [Ca2+](i) returned to near basal values within 3-5 min. Devazepide but not YMM022 inhibited this [Ca2+](i) response. Low doses of CCK-8 stimulate duodenal alkaline secretion and induce enterocyte [Ca2+](i) signaling by an action at CCK1 receptors. The results point to importance of CCK in the rapid postprandial rise in mucosa-protective duodenal secretion.
Place, publisher, year, edition, pages
2013. Vol. 183, 46-53 p.
Duodenal enterocytes, Fed and fasting state, Galanin, Gastrin, Luzindole
Natural Sciences Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-202923DOI: 10.1016/j.regpep.2013.03.008ISI: 000319244500009OAI: oai:DiVA.org:uu-202923DiVA: diva2:634526