Molecular cloning, expression and pharmacological characterization of the canine cholecystokinin 1 receptor

Morton, Magda F.; Pyati, Jayashree; Dai, Heng; Li, Lina; Moreno, Veronica; Shankley, Nigel P.

doi:10.1038/sj.bjp.0706196

Cited by 11 publications

(11 citation statements)

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“…As far as we are aware, the mechanism of this ‘tachyphylaxis’ has not been established, however, there are a number of differences between JNJ‐26070109 and YF476. These include the observation that while YF476 has very high affinity for the human CCK 2 receptor, it is only ∼60‐fold selective over the related human CCK 1 receptor, whereas JNJ‐26070109 is >1200‐fold selective for the human CCK 2 over the CCK 1 receptor (Morton et al ., 2005a,b; 2011b). This may be of functional significance as gastrin/cholecystokinin dual knockout mice have a phenotype where acid secretion is similar to controls.…”

Section: Discussionmentioning

confidence: 99%

The cholecystokinin CCK₂ receptor antagonist, JNJ‐26070109, inhibits gastric acid secretion and prevents omeprazole‐induced acid rebound in the rat

Barrett

Lagaud

Wagaman

et al. 2012

British J Pharmacology

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Chronic administration of JNJ-26070109 effectively inhibited gastric acid secretion and suppressed proton pump inhibitor (PPI)-induced acid rebound in the rat. This work advances the field by demonstrating that modest doses of a competitive CCK(2) receptor antagonist have significant and functionally important anti-trophic actions in the gastric mucosa. These properties make JNJ-26070109 a suitable candidate for clinical investigation for the treatment of GORD.

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Section: Discussionmentioning

confidence: 99%

The cholecystokinin CCK₂ receptor antagonist, JNJ‐26070109, inhibits gastric acid secretion and prevents omeprazole‐induced acid rebound in the rat

Barrett

Lagaud

Wagaman

et al. 2012

British J Pharmacology

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“…Rabbit CCK1R is 92% homologous (87% identity) to the rat CCK1R sequence (8,119). Canine gallbladder CCK1R is 89% identical to the human and 85% identical to the rat CCK1R (97). Different animal species share ϳ90% identity in their CCK1R amino acid sequence (102).…”

Section: Cck Receptor In Different Animal Speciesmentioning

confidence: 90%

How does cholecystokinin stimulate exocrine pancreatic secretion? From birds, rodents, to humans

Wang¹,

Cui²

2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Wang BJ, Cui ZJ. How does cholecystokinin stimulate exocrine pancreatic secretion? From birds, rodents, to humans. Am J Physiol Regul Integr Comp Physiol 292: R666-R678, 2007. First published October 19, 2006; doi:10.1152/ajpregu.00131.2006.-The field of cholecystokinin (CCK) stimulation of exocrine pancreatic secretion has experienced major changes in the recent past. This review attempts to summarize the present status of the field. CCK production in the intestinal I cells, the molecular forms of CCK produced and subsequently circulated in the blood, the presence or absence of CCK receptors on the isolated pancreatic acinar cells and the associated signaling for acinar cell secretion, and the actual circuits and sites of action for CCK regulation of exocrine pancreatic secretion in vivo are reviewed in different animal species with an emphasis on birds, rodents, and humans. Clear differences in the relative importance of neural and direct modes of CCK action on pancreatic acinar cells were identified. Rodents seem to be endowed with both modes of action, whereas in humans the neural mode may predominate. In birds, such as duck, the direct mode needs further assistance from pituitary adenylate cyclaseactivating peptide/VIP receptors. However, much further work needs to be directed to the neural mode to map out all sites of CCK action and details of the full circuits, and we foresee a major revival for this field of research in the near future. pancreatic acinar cells; vagal afferent nerves; plasma cholecystokinin concentration; species specificity IT IS GENERALLY ACCEPTED THAT cholecystokinin (CCK) as a gut hormone is an important endogenous secretagogue in exocrine pancreatic secretion. CCK also stimulates gallbladder contraction and enhances growth of the exocrine pancreas (63,115,138). CCK is produced and released by the intestinal mucosal I cells (78). This source of CCK may travel through the circulation to target tissues that include the exocrine pancreas and gallbladder (65,78). CCK peptides are also found in large quantities in neurons, but neuronal CCK contributes negligibly to CCK concentration in the circulation (118). This general picture has been changed drastically by the recent findings that CCK can also stimulate exocrine pancreatic secretion by the excitation of sensory nerves and vagovagal and enteropancreatic reflexes, and this may be the only pathway in humans (65, 105). In addition, major differences have been found in the traditional humoral pathway, depending on the animal species (35,149). Therefore, the purpose of this review is to present the current status of CCK regulation of exocrine pancreatic secretion with a particular emphasis on species specificity as shown in birds, rodents, and humans.

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“…At the time, however, the affinity of these antagonists to the canine CCK1 receptors had not been systematically evaluated and thus the actual selectivity was unknown. Recently, it was demonstrated that L-364,718 expresses about 60-fold increased affinity at the canine CCK1 over the canine CCK2 receptors by cloning the canine CCK1 receptor and subsequent pharmacological analysis of the CCK receptor ligands, and therefore can be considered CCK1 receptor-selective in dogs and humans (Morton et al, 2005).…”

Section: Role Of Cck and Cck Receptorsmentioning

confidence: 99%

Secretion from acinar cells of the exocrine pancreas: Role of enteropancreatic reflexes and cholecystokinin

Singer

Niebergall-Roth

2009

Cell Biology International

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Although the molecular machinery and mechanism of cell secretion in acinar cells of the exocrine pancreas is well documented and clear, only recently has the pharmacophysiology of pancreatic exocrine secretion come to light. Therefore, we focus in this article on the current understanding of the pharmacophysiology of pancreatic exocrine secretion. The pancreatic secretory response to ingestion of a meal is mediated via a complex interplay of neural, humoral and paracrine mediators. A major role in the control of the intestinal phase of pancreatic secretion is attributed to vago-vagal enteropancreatic reflexes. In the scheme of this control mechanism, afferents originating in the duodenal mucosa, and efferents mediating central input on the pancreatic ganglia, activate intrapancreatic postganglionic neurons. Experiments utilizing specific receptor antagonists demonstrate the involvement of both muscarinic M1 and M3 receptors expressed in pancreatic acinar cells. Cholecystokinin (CCK), originally implicated in the humoral secretion of pancreatic enzymes, through a direct action on acinar CCK receptors, is also essential to the enteropancreatic reflex mechanism. CCK stimulation of the exocrine pancreatic secretion through excitation of sensory afferents of the enteropancreatic reflexes, is a paracrine mode of CCK action, and is probably the only one in humans and the predominant one in rats. In dogs, however, CCK acts on the pancreas via both the humoral and a paracrine route. More recent experiments suggest further possible sites of CCK action. Additionally, at the brain stem, vago-vagal enteropancreatic reflexes may be modulated by input from higher brain centres, particularly the hypothalamic-cholinergic system in the tonic stimulation of preganglionic neurons of the dorsal motor nucleus of the vagus projecting into the pancreas.

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Molecular cloning, expression and pharmacological characterization of the canine cholecystokinin 1 receptor

Cited by 11 publications

References 24 publications

The cholecystokinin CCK₂ receptor antagonist, JNJ‐26070109, inhibits gastric acid secretion and prevents omeprazole‐induced acid rebound in the rat

The cholecystokinin CCK₂ receptor antagonist, JNJ‐26070109, inhibits gastric acid secretion and prevents omeprazole‐induced acid rebound in the rat

How does cholecystokinin stimulate exocrine pancreatic secretion? From birds, rodents, to humans

Secretion from acinar cells of the exocrine pancreas: Role of enteropancreatic reflexes and cholecystokinin

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Molecular cloning, expression and pharmacological characterization of the canine cholecystokinin 1 receptor

Cited by 11 publications

References 24 publications

The cholecystokinin CCK2 receptor antagonist, JNJ‐26070109, inhibits gastric acid secretion and prevents omeprazole‐induced acid rebound in the rat

The cholecystokinin CCK2 receptor antagonist, JNJ‐26070109, inhibits gastric acid secretion and prevents omeprazole‐induced acid rebound in the rat

How does cholecystokinin stimulate exocrine pancreatic secretion? From birds, rodents, to humans

Secretion from acinar cells of the exocrine pancreas: Role of enteropancreatic reflexes and cholecystokinin

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The cholecystokinin CCK₂ receptor antagonist, JNJ‐26070109, inhibits gastric acid secretion and prevents omeprazole‐induced acid rebound in the rat

The cholecystokinin CCK₂ receptor antagonist, JNJ‐26070109, inhibits gastric acid secretion and prevents omeprazole‐induced acid rebound in the rat