The feeding responses evoked by endogenous cholecystokinin are regulated by different gastrointestinal sites

Washington, Martha C.; Williams, Kasey E.; Sayegh, Ayman I.

doi:10.1016/j.yhbeh.2015.10.019

Cited by 19 publications

(17 citation statements)

References 22 publications

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“…CCK binding to CCK1Rs present on vagal afferent neurons within the wall of the intestine could be an early event, not influenced by differential extraction of different forms of hormone from the portal circulation. This is supported by studies in which very low doses of CCK-58 were administered locally into small vessels within the gut wall and shown to elicit reduced food intake, while similar systemic infusions had no effect [29–32]. This was reproduced with luminal infusion of the non-nutrient trypsin inhibitor, camostat, to stimulate release of endogenous CCK.…”

Section: Ligand-directed Bias In Signalingmentioning

confidence: 83%

“…This powerful approach was also applied to selective infusions into the celiac artery (supplying splenic, left gastric and common hepatic arteries) and the more distal cranial mesenteric artery (supplying pancreatico-duodenal, jejunal, and ileocolic arteries), with the former responsible for regulating meal size, while the latter was responsible for regulating inter-meal interval [31, 32]. CCK1R-bearing vagal afferent neurons are present in both vascular distributions, but it is fascinating that regulation of meal size is an event that appears to be regulated higher in the gut than regulation of the inter-meal interval.…”

Section: Ligand-directed Bias In Signalingmentioning

confidence: 99%

“…Indeed, CCK affects all these events, with impact on pylorus to slow gastric emptying if too much food is entering the small bowel, with a stimulatory impact on gallbladder emptying to contribute to micelle formation critical for fat emulsification, and with stimulatory effects on secretion of pancreatic zymogens for digestion of complex nutrients. Of particular interest, recent studies reviewed above [31, 32] suggest that even within the “proximal gut,” CCK may include spatial differences in action, with the most proximal events stimulated by CCK acting at CCK1Rs contributing to limiting meal size, and the more distal events stimulated by this same hormone and receptor contributing to extending the inter-meal interval. In evolution, it has been more of a challenge to ensure adequate nutrition, than to prevent excessive feeding.…”

Section: Benefits Of Combination Therapiesmentioning

confidence: 99%

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Metabolic Actions of the Type 1 Cholecystokinin Receptor: Its Potential as a Therapeutic Target

Miller

Desai

2016

Trends in Endocrinology & Metabolism

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Cholecystokinin regulates appetite and reduces food intake by activating the type 1 CCK receptor (CCK1R). Attempts to develop CCK1R agonists for obesity have yielded active agents that have not reached clinical practice. In this review we discuss why, along with new strategies to target CCK1R more effectively. We examine signaling events and the possibility of developing agents that exhibit ligand-directed bias, to dissociate satiety activity from undesirable side effects. Potential allosteric sites of modulation are also reviewed, along with desired properties of a positive allosteric modulator without intrinsic agonist action as another strategy to treat obesity. These new types of CCK1R-active drugs could be useful as stand-alone agents or as part of a rational drug combination for management of obesity.

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Section: Ligand-directed Bias In Signalingmentioning

confidence: 83%

Section: Ligand-directed Bias In Signalingmentioning

confidence: 99%

Section: Benefits Of Combination Therapiesmentioning

confidence: 99%

See 1 more Smart Citation

Metabolic Actions of the Type 1 Cholecystokinin Receptor: Its Potential as a Therapeutic Target

Miller

Desai

2016

Trends in Endocrinology & Metabolism

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“…It has been demonstrated as a central regulator of neuronal circuits. It plays vital roles in the gastrointestinal system, satiation, memory, anxiety-related behaviors, and other neuropsychiatric disorders [Lee and Soltesz, 2011;Zwanzger et al, 2012;Nishimura et al, 2015;Washington et al, 2016]. Finally, we identified LGI2 (OMIM 608301) as another candidate gene.…”

Section: Discussionmentioning

confidence: 99%

A Rare de novo Interstitial Duplication at 4p15.2 in a Boy with Severe Congenital Heart Defects, Limb Anomalies, Hypogonadism, and Global Developmental Delay

Liang

Xie²,

Shen³

et al. 2016

Cytogenet Genome Res

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Proximal 4p deletion syndrome is a relatively rare genetic condition characterized by dysmorphic facial features, limb anomalies, minor congenital heart defects, hypogonadism, cafe-au-lait spots, developmental delay, tall and thin habitus, and intellectual disability. At present, over 20 cases of this syndrome have been published. However, duplication of the same region in proximal 4p has never been reported. Here, we describe a 2-year-5-month-old boy with severe congenital heart defects, limb anomalies, hypogonadism, distinctive facial features, pre- and postnatal developmental delay, and mild cognitive impairments. A de novo 4.5-Mb interstitial duplication at 4p15.2p15.1 was detected by chromosomal microarray analysis. Next-generation sequencing was employed and confirmed the duplication, but revealed no additional pathogenic variants. Several candidate genes in this interval responsible for the complex clinical phenotype were identified, such as RBPJ, STIM2, CCKAR, and LGI2. The results suggest a novel contiguous gene duplication syndrome.

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“…One catheter was implanted in each rat, and the meal patterns (meal was consumption of ≥ 0.2 g, and intermeal interval [IMI] was no feeding activity for ≥ 15 min), were done as described in details previously (Sayegh et al, 2015; Washington et al, 2014a; Washington et al, 2015; Williams et al, 2016). …”

Section: Methodsmentioning

confidence: 99%

The BB2 receptor antagonist BW2258U89 attenuates the feeding responses evoked by exogenous gastrin releasing peptide-29

Washington

Mhalhal

Sayegh

2016

Hormones and Behavior

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This confirmatory work is aimed to test that the hypothesis that the gastrin releasing peptide (GRP) receptor – the BB2 receptor – is necessary for reduction of meal size (MS) and prolongation of the intermeal interval (IMI) by the small and the large forms of GRP in the rat, GRP-10 and GRP-29, and to confirm the sites of action regulating such responses – the vascular bed of the celiac artery (CA, supplying stomach and upper duodenum). To pursue these aims we measured first MS and IMI length in response to GRP-10 and GRP-29 (0, 0.5 nmol/kg) infused in the CA (n=8 rats) and the cranial mesenteric artery (CMA, supplying the small and part of the large intestine, n=8 rats) in near spontaneously free feeding rats pretreated with the BB2 receptor antagonist BW2258U89 (0.1 mg/kg) in the same arteries prior to the onset of the dark cycle. We found that GRP-29, but not GRP-10, infused by the CA reduced MS and prolonged the IMI by decreasing meal latency and meal duration and the BB2 receptor antagonist BW2258U89 infused in the same artery attenuated these responses. These results suggest that the BB2 receptor is necessary for reduction of MS and prolongation of the IMI by exogenous GRP-29, and the vascular bed of the CA, stomach and upper duodenum, contains sites of action regulating these feeding responses.

show abstract

The feeding responses evoked by endogenous cholecystokinin are regulated by different gastrointestinal sites

Cited by 19 publications

References 22 publications

Metabolic Actions of the Type 1 Cholecystokinin Receptor: Its Potential as a Therapeutic Target

Metabolic Actions of the Type 1 Cholecystokinin Receptor: Its Potential as a Therapeutic Target

A Rare de novo Interstitial Duplication at 4p15.2 in a Boy with Severe Congenital Heart Defects, Limb Anomalies, Hypogonadism, and Global Developmental Delay

The BB2 receptor antagonist BW2258U89 attenuates the feeding responses evoked by exogenous gastrin releasing peptide-29

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