Cholecystokinin and Gastrin Receptors

Dufresne, Marlène; Seva, Catherine; Fourmy, Daniel

doi:10.1152/physrev.00014.2005

Cited by 417 publications

(431 citation statements)

References 575 publications

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“…CCK and gastrin exert their activities through specific interaction with two cognate receptors, CCK1 (CCK1R) and CCK2R (Dufresne et al 2006). CCK1R is a CCK-specific receptor, and sulfation of CCK is required for binding to CCK1R.…”

Section: Introductionmentioning

confidence: 99%

Molecular and functional characterization of cionin receptors in the ascidian, Ciona intestinalis: the evolutionary origin of the vertebrate cholecystokinin/gastrin family

Sekiguchi

Ogasawara²,

Satake³

2012

Journal of Endocrinology

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Cholecystokinin (CCK) and gastrin are vertebrate brain-gut peptides featured by a sulfated tyrosine residue and a C-terminally amidated tetrapeptide consensus sequence. Cionin, identified in the ascidian, Ciona intestinalis, the closest species to vertebrates, harbors two sulfated tyrosines and the CCK/gastrin consensus tetrapeptide sequence. While a putative cionin receptor, cior, was cloned, the ligand-receptor relationship between cionin and CioR remains unidentified. Here, we identify two cionin receptors, CioR1 and CioR2, which are the aforementioned putative cionin receptor and its novel paralog respectively. Phylogenetic analysis revealed that CioRs are homologous to vertebrate CCK receptors (CCKRs) and diverged from a common ancestor in the Ciona-specific lineage. Cionin activates intracellular calcium mobilization in cultured cells expressing CioR1 or CioR2. Monosulfated and nonsulfated cionin exhibited less potent or no activity, indicating that CioRs possess pharmacological features similar to the vertebrate CCK-specific receptor CCK1R, rather than its subtype CCK2R, given that a sulfated tyrosine in CCK is required for binding to CCK1R, but not to CCK2R. Collectively, the present data reveal that CioRs share a common ancestor with vertebrate CCKRs and indicate that CCK and CCK1R form the ancestral ligand-receptor pair in the vertebrate CCK/gastrin system. Cionin is expressed in the neural complex, digestive organs, oral siphon and atrial siphons, whereas the expression of ciors was detected mainly in these tissues and the ovary. Furthermore, cioninergic neurons innervate both of the siphons. These results suggest that cionin is involved in the regulation of siphonal functions.

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Section: Introductionmentioning

confidence: 99%

Molecular and functional characterization of cionin receptors in the ascidian, Ciona intestinalis: the evolutionary origin of the vertebrate cholecystokinin/gastrin family

Sekiguchi

Ogasawara²,

Satake³

2012

Journal of Endocrinology

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“…However, differentiating mESCs (ie, growing without LIF) treated with gastrin also did not display enhanced levels of Reg1 albeit their expression of CCK2R. It is possible that downstream mediators of gastrin signaling relayed by CCK2R [ 54 ] may be unavailable in mESCs and their immediate committed progeny. A link between the canonical Wnt signaling and Reg gene/ protein expression has been suggested previously.…”

Section: Discussionmentioning

confidence: 97%

Expression of Reg Family Proteins in Embryonic Stem Cells and Its Modulation by Wnt/β-Catenin Signaling

Jing

Kehoe

Tzanakakis

2010

Stem Cells and Development

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Regenerating islet (Reg) proteins are involved in the proliferation and differentiation of diverse cell types. However, whether embryonic stem cells (ESCs) express Reg genes and their corresponding proteins remains unknown. In this study, we probed the expression of Reg family members by mouse ESCs (mESCs). Mouse Reg1 and Reg3γ were detected in undifferentiated stem cells. Furthermore, we tested if gastrin-an inducer of Reg1 expression in committed cells-up-regulates the Reg1 gene in mESCs. Gastrin did not affect the expression of Reg1 either in self-renewing mESCs or under conditions permitting their differentiation. Moreover, overexpression of Reg genes found in various forms of cancer has been linked to dysregulated activation of the canonical Wnt/β-catenin cascade. Given the important roles of Wnt signaling in stem cells, we investigated if activation of Wnt alters the expression of Reg genes in mESCs. Wnt activation led to an increase in Reg1 gene expression with a concomitant increase in the amount of secreted Reg1 protein. Finally, the expression pattern of genes indicative of differentiation was examined in mESCs that were either exposed to soluble Reg1 or overexpressed the Reg1 gene. This is the fi rst account of expression of Reg family members by ESCs. Our results show that the canonical Wnt cascade affects Reg expression and warrants further studies into the potential roles of Reg proteins in stem cell physiology.

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“…Second, peripheral injection of PYY3-36 increases c-fos expression, a marker of neuronal activation, in the arcuate nucleus [97]. Third, PYY3-36 has no effect on food intake in Y2R-knockout mice [ 133] with several effects, including gallbladder contraction, sphincter of Oddi relaxation, pancreatic enzyme release and somatostatin release [134].…”

Section: Peptide Yymentioning

confidence: 99%

Obesity treatment: novel peripheral targets

Field¹,

Chaudhri²,

Bloom³

2009

Brit J Clinical Pharma

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Our knowledge of the complex mechanisms underlying energy homeostasis has expanded enormously in recent years. Food intake and body weight are tightly regulated by the hypothalamus, brainstem and reward circuits, on the basis both of cognitive inputs and of diverse humoral and neuronal signals of nutritional status. Several gut hormones, including cholecystokinin, glucagon-like peptide-1, peptide YY, oxyntomodulin, amylin, pancreatic polypeptide and ghrelin, have been shown to play an important role in regulating short-term food intake. These hormones therefore represent potential targets in the development of novel anti-obesity drugs. This review focuses on the role of gut hormones in short-and long-term regulation of food intake, and on the current state of development of gut hormone-based obesity therapies.

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Cholecystokinin and Gastrin Receptors

Cited by 417 publications

References 575 publications

Molecular and functional characterization of cionin receptors in the ascidian, Ciona intestinalis: the evolutionary origin of the vertebrate cholecystokinin/gastrin family

Molecular and functional characterization of cionin receptors in the ascidian, Ciona intestinalis: the evolutionary origin of the vertebrate cholecystokinin/gastrin family

Expression of Reg Family Proteins in Embryonic Stem Cells and Its Modulation by Wnt/β-Catenin Signaling

Obesity treatment: novel peripheral targets

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