title: Cholecystokinin but not ghrelin stimulates mucosal bicarbonate secretion in rat duodenum: independence of feeding status and cholinergic stimuli.
abstract: 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 ([Ca(2+)]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 [Ca(2+)]i signaling in acutely isolated duodenal enterocytes. After an initial peak response, [Ca(2+)]i returned to near basal values within 3-5min. Devazepide but not YMM022 inhibited this [Ca(2+)]i response. Low doses of CCK-8 stimulate duodenal alkaline secretion and induce enterocyte [Ca(2+)]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.
authors.affiliation: Department of Neuroscience, Division of Physiology, Uppsala University, Uppsala, Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Sjöblom
authors.affiliation: Department of Neuroscience, Division of Physiology, Uppsala University, Uppsala, Sweden.
authors.forename: Ramin
authors.initials: R
authors.lastname: Lindqvist
authors.affiliation: Department of Neuroscience, Division of Physiology, Uppsala University, Uppsala, Sweden.
authors.forename: Magnus W
authors.initials: MW
authors.lastname: Bengtsson
authors.affiliation: Department of Neuroscience, Division of Physiology, Uppsala University, Uppsala, Sweden.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Jedstedt
authors.affiliation: Department of Neuroscience, Division of Physiology, Uppsala University, Uppsala, Sweden. Electronic address: gunnar.flemstrom@neuro.uu.se.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Flemström
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D018678:Cholinergic Agents / Q000494:pharmacology*; D020109:Devazepide / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism*; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism; D054439:Ghrelin / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism; D012844:Sincalide / Q000494:pharmacology*
chemical_list: D001639:Bicarbonates; D018678:Cholinergic Agents; D054439:Ghrelin; D011949:Receptors, Cholecystokinin; D020109:Devazepide; D012844:Sincalide; D002118:Calcium