title: Cholecystokinin pathways modulate sensations induced by gastric distension in humans.
abstract: Ingested fat releases CCK, causes gastric relaxation, delays gastric emptying, and limits meal size; however, the mechanistic link among these actions has not been established. Fatty acid release of CCK is chain-length sensitive; dodecanoic acid (C12) induces greater CCK release than decanoic acid (C10). The effect of C12 or C10 on tolerance to subsequent intragastric infusion of liquid was determined in healthy subjects, with and without the CCK(1) receptor antagonist dexloxiglumide. Gastric wall relaxation after either fatty acid was assessed by graded volume distension and by barostat; gastric emptying was measured by gastric aspiration and by a [(13)C]octanoic acid breath technique. C12 released more CCK (mean plasma CCK after vehicle, 4.7 +/- 0.8 pM; C10, 4.8 +/- 0.3 pM; C12, 8 +/- 1.2 pM; P < 0.05 C12 vs. C10 or vehicle) and reduced the volume of water (and of 5 and 25% glucose solutions) delivered at maximum tolerance compared with C10 or vehicle (volume of water tolerated after vehicle, 1,535 +/- 164 ml; C10, 1,335 +/- 160 ml; C12, 842 +/- 103 ml; P < 0.05 C12 vs. C10 or vehicle); this effect was abolished by dexloxiglumide. Intragastric volumes were always similar at the limit of tolerance, and, whereas gastric relaxation occurred to similar degrees after the fatty acids, its duration was longer after C12, which also induced a longer delay in half-gastric emptying [t(1/2)(min) after vehicle, 53 +/- 2; C10, 67 +/- 3; C12, 88 +/- 7; P < 0.05 C12 vs. C10 or vehicle]. In conclusion, ingestion of a CCK-releasing fatty acid reduces the tolerated volume of liquid delivered into the stomach, primarily via a CCK(1) receptor-mediated delay in gastric emptying.
authors.affiliation: Gastro-Intestinal Science Group, Hope Hospital, University of Manchester, Salford M6 8HD, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Lal
authors.forename: John
authors.initials: J
authors.lastname: McLaughlin
authors.forename: Josephine
authors.initials: J
authors.lastname: Barlow
authors.forename: Massimo
authors.initials: M
authors.lastname: D'Amato
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Giacovelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Varro
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Dockray
authors.forename: David G
authors.initials: DG
authors.lastname: Thompson
mesh_terms: D000328:Adult; D002404:Catheterization; D002648:Child; D002766:Cholecystokinin / Q000378:metabolism*; D003652:Decanoic Acids / Q000494:pharmacology; D004326:Drinking; D004548:Elasticity; D004655:Emulsions; D005227:Fatty Acids / Q000494:pharmacology; D005746:Gastric Emptying / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D007223:Infant; D007441:Intubation, Gastrointestinal; D007850:Lauric Acids / Q000494:pharmacology; D008875:Middle Aged; D011312:Pressure; D012677:Sensation; D016037:Single-Blind Method; D013270:Stomach / Q000187:drug effects / Q000502:physiology*
chemical_list: D003652:Decanoic Acids; D004655:Emulsions; D005227:Fatty Acids; D007850:Lauric Acids; C030358:lauric acid; C031071:decanoic acid; D002766:Cholecystokinin; D005947:Glucose