Response of the gastric vagal afferent activity to cholecystokinin in rats lacking type A cholecystokinin receptors (original) (raw)
Related papers
Regulatory Peptides, 1994
The aim of these experiments was to characterize the receptor affinity state through which CCK produces pyloric contraction and inhibits gastric emptying in the rat using the novel CCK heptapeptide analog CCK-JMV-180. CCK-JMV-180 has been demonstrated to act as a functional agonist at high affinity pancreatic CCK A receptors but as a functional antagonist at CCK A low affinity receptors. CCK-8 (1, 3.2 and 10 nM) induced dose dependent tension increases in isolated pyloric segments. CCK-JMV-180 (3.2/aM) or vehicle failed to mimic this action when administered alone but blocked the ability of CCK-8 (3.2 nM) to induce tension increases. CCK-8 (2/~g/kg) also inhibited the gastric emptying of physiological saline. CCK-JMV-180 (320 and 1000/~g/kg) failed to inhibit emptying when administered alone but dose dependently antagonized CCK induced inhibition of gastric emptying. Thus, in both preparations CCK-JMV-180 acted as a functional CCK antagonist. This profile is consistent with the interpretation that the actions of CCK in pyloric contraction and the inhibition of gastric emptying are mediated through CCK's interactions with receptors functionally similar to pancreatic low affinity sites.
Autoradiographic and functional development of gastric cholecystokinin receptors in the rat
Peptides, 1990
To determine the functional role for and the pharmacological specificity of developing gastrointestinal CCK receptors, in vitro pyloric contractility and autoradiographic CCK receptor binding were examined in pups aged 1-20 days. CCK contracted the gastroduodenal junction at all ages, while nonsulfated CCK-8 (d-CCK) was less potent. Autoradiographic studies revealed CCK binding localized to the gastroduodenal junction throughout development. MK-329, a specific type A CCK receptor antagonist, completely displaced lzsI CCK-8 binding at all ages, while d-CCK displaced binding at ages at which d-CCK elicited gastroduodenal contractility. The results demonstrate a physiological role for and pharmacological specificity of neonatal gastroduodenal CCK receptors.
Annals of the New York Academy of Sciences, 1985
Cholecystokinin (CCK) reduces feeding in a number of species, including man. Several loci have been proposed for this action, including the vagus nerve, pyloric sphincter, and brain, all of which bear CCK receptors. Gastric vagotomy blocks the inhibitory effect of CCK on food intake suggesting the gastric vagus as a possible locus of action. CCK inhibits gastric emptying, and, in the monkey, the satiety effect at threshold doses may only be demonstrable when the stomach has been distended with saline, suggesting that CCK may be acting through its gastric inhibitory effect to modify food intake. Developmental studies of CCK receptors in the rat brain have shown very low levels at birth.' Accordingly, the demonstration of an inhibitory effect of CCK on ingestion and of receptor sites for CCK in the periphery in neonatal rat pups would be evidence in favor of a peripheral locus of action. In the present study, this question was addressed by an investigation of the distribution of gut receptor sites for CCK and of the effect of CCK on independent ingestion and on gastric emptying in neonatal rat pups.
Effect of CCK and its antagonists on gastric emptying
Journal of Physiology-Paris, 1993
-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.