Effect of CCK and its antagonists on gastric emptying.
Cholecystokinin (CCK) belongs to the group of substances known as brain-gut peptides: it functions both as a neuropeptide and a gut hormone. The peptide and its synthetic derivatives (like for instance CCK-8 and the amphibian counterpart caerulein) significantly delay emptying of gastric contents in both animals and humans. The fact that CCK, in doses mimicking postprandial plasma levels, strongly affects emptying rate suggests the peptide to be a physiologic regulator of gastric emptying. Unfortunately, clear definition of the role of CCK in the physiology of gastric motor activity has long been hampered by the lack of specific and potent non-peptide antagonists of CCK-receptors. The availability of such compounds has stimulated a broad array of investigations into the physiological actions of this hormone and examination of its putative role in certain diseases. This paper summarizes the available data concerning the effect of CCK and its antagonists on gastric emptying. The use of selective CCK-antagonists has allowed to establish that the gastric motor effect of the peptide is direct and mediated through the stimulation of CCK-A receptors. As a consequence, CCK-A antagonism results in acceleration of emptying rate under certain experimental and clinical conditions. This peculiar pharmacologic effect of CCK-A antagonists, which could be useful in the treatment of functional dyspepsia (idiopathic or diabetic), gastroparesis and gastro-esophageal reflux disease (where patients often display a delayed emptying rate of solid food) needs to be further investigated, in order to fully explore their potential as gastrokinetic drugs.
Scarpignato
C
C
Institute of Pharmacology, School of Medicine & Dentistry, Maggiore University Hospital, University of Parma, Italy.
Varga
G
G
Corradi
C
C
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D001921:Brain / Q000378:metabolism / Q000502:physiology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D020109:Devazepide; D005746:Gastric Emptying / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects; D006801:Humans; D011949:Receptors, Cholecystokinin / Q000378:metabolism / Q000502:physiology; D012844:Sincalide / Q000378:metabolism; D013758:Tetragastrin / Q000378:metabolism
D001570:Benzodiazepinones; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; D002766:Cholecystokinin; D020109:Devazepide; D012844:Sincalide