Cholecystokinin Regulates Expression of Y2 Receptors in Vagal Afferent Neurons Serving the Stomach

Burdyga, Galina; Lartigue, Guillaume de; Raybould, Helen E.; Morris, Richard; Dimaline, R.; Varró, Andrea; Thompson, David G.; Dockray, Graham J.

doi:10.1523/jneurosci.2493-08.2008

Cited by 79 publications

(86 citation statements)

References 44 publications

(77 reference statements)

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“…Therefore, the intermediate submucosal samples were not used for further experiments in order to simplify the analysis (data not shown). CCK-1 , NPYY2, and NPYY4 receptors are class A GPCRs for neuroendocrine peptides such as CCK, peptide YY (PYY), and pancreatic polypeptide (PP), which exist on vagal primary afferent fibers innervating the GI tract in rats and humans (Burdyga et al 2008;Koda et al 2005;Cummings and Overduin 2007). Consistent with previous studies on rats and humans, the mRNA of these receptors was predominantly expressed in the muscle-myenteric nerve layer (Fig.…”

Section: Expression Profiles Of Gi-related Gpcrssupporting

confidence: 84%

Anatomical and histological profiling of orphan G-protein-coupled receptor expression in gastrointestinal tract of C57BL/6J mice

et al. 2009

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G-protein-coupled receptors (GPCRs) constitute the largest family of transmembrane receptors and regulate a variety of physiological and disease processes. Although the roles of many non-odorant GPCRs have been identified in vivo, several GPCRs remain orphans (oGPCRs). The gastrointestinal (GI) tract is the largest endocrine organ and is a promising target for drug discovery. Given their close link to physiological function, the anatomical and histological expression profiles of benchmark GI-related GPCRs, such as the cholecystokinin-1 receptor and GPR120, and 106 oGPCRs were investigated in the mucosal and muscle-myenteric nerve layers in the GI tract of C57BL/6J mice by quantitative real-time polymerase chain reaction. The mRNA expression patterns of these benchmark molecules were consistent with previous in situ hybridization and immunohistochemical studies, validating the experimental protocols in this study. Of 96 oGPCRs with significant mRNA expression in the GI tract, several oGPCRs showed unique expression patterns. GPR85, GPR37, GPR37L1, brain-specific angiogenesis inhibitor (BAI) 1, BAI2, BAI3, and GPRC5B mRNAs were preferentially expressed in the muscle-myenteric nerve layer, similar to GPCRs that are expressed in both the central and enteric nerve systems and that play multiple regulatory roles throughout the gut-brain axis. In contrast, GPR112, trace amine-associated receptor (TAAR) 1, TAAR2, and GPRC5A mRNAs were preferentially expressed in the mucosal layer, suggesting their potential roles in the regulation of secretion, immunity, and epithelial homeostasis. These anatomical and histological mRNA expression profiles of oGPCRs provide useful clues about the physiological roles of oGPCRs in the GI tract.

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Section: Expression Profiles Of Gi-related Gpcrssupporting

confidence: 84%

Anatomical and histological profiling of orphan G-protein-coupled receptor expression in gastrointestinal tract of C57BL/6J mice

et al. 2009

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“…Our data are in close agreement with two prior studies. Burdyga et al (8) reported that among NG neurons projecting to the stomach identified via retrograde labeling, 70 -80% of the population exhibited CCK-R A immunoreactivity, and we previously reported by use of single-cell calcium measurements that 74% of neurons labeled from the stomach responded to CCK (37). In our previous study we also reported that 71% of duodenal innervating neurons responded to CCK, whereas in the present study we find a value of 60%.…”

Section: Discussionsupporting

confidence: 55%

Expression of transient receptor potential channels and two-pore potassium channels in subtypes of vagal afferent neurons in rat

Zhao

Sprunger

Simasko

2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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Vagal afferent neurons relay important information regarding the control of the gastrointestinal system. However, the ionic mechanisms that underlie vagal activation induced by sensory inputs are not completely understood. We postulate that transient receptor potential (TRP) channels and/or two-pore potassium (K2p) channels are targets for activating vagal afferents. In this study we explored the distribution of these channels in vagal afferents by quantitative PCR after a capsaicin treatment to eliminate capsaicin-sensitive neurons, and by single-cell PCR measurements in vagal afferent neurons cultured after retrograde labeling from the stomach or duodenum. We found that TRPC1/3/5/6, TRPV1-4, TRPM8, TRPA1, TWIK2, TRAAK, TREK1, and TASK1/2 were all present in rat nodose ganglia. Both lesion results and single-cell PCR results suggested that TRPA1 and TRPC1 were preferentially expressed in neurons that were either capsaicin sensitive or TRPV1 positive. Expression of TRPM8 varied dynamically after various manipulations, which perhaps explains the disparate results obtained by different investigators. Last, we also examined ion channel distribution with the A-type CCK receptor (CCK-R(A)) and found there was a significant preference for neurons that express TRAAK to also express CCK-R(A), especially in gut-innervating neurons. These findings, combined with findings from prior studies, demonstrated that background conductances such as TRPC1, TRPA1, and TRAAK are indeed differentially distributed in the nodose ganglia, and not only do they segregate with specific markers, but the degree of overlap is also dependent on the innervation target.

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“…A number of receptors have been found to be differentially expressed in VAN depending on the feeding state of the animal (6 -10); however, TLR4 expression was unchanged in cultured VAN under conditions that mimic feeding and fasting in vivo (6,14). LPS has been found to induce SOCS-3 expression in macrophage and microglia (33), leading us to hypothesize that LPS induce SOCS-3 expression in VAN, thereby resulting in leptin resistance in these neurons.…”

Section: Discussionmentioning

confidence: 99%

Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons

Lartigue

Serre

Espero

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

151

142

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de Lartigue G, Barbier de la Serre C, Espero E, Lee J, Raybould HE. Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons. Am J Physiol Endocrinol Metab 301: E187-E195, 2011. First published April 26, 2011; doi:10.1152/ajpendo.00056.2011.-Ingestion of high-fat, high-calorie diets is associated with hyperphagia, increased body fat, and obesity. The mechanisms responsible are currently unclear; however, altered leptin signaling may be an important factor. Vagal afferent neurons (VAN) integrate signals from the gut in response to ingestion of nutrients and express leptin receptors. Therefore, we tested the hypothesis that leptin resistance occurs in VAN in response to a high-fat diet. Sprague-Dawley rats, which exhibit a bimodal distribution of body weight gain, were used after ingestion of a high-fat diet for 8 wk. Body weight, food intake, and plasma leptin levels were measured. Leptin signaling was determined by immunohistochemical localization of phosphorylated STAT3 (pSTAT3) in cultured VAN and by quantifaction of pSTAT3 protein levels by Western blot analysis in nodose ganglia and arcuate nucleus in vivo. To determine the mechanism of leptin resistance in nodose ganglia, cultured VAN were stimulated with leptin alone or with lipopolysaccharide (LPS) and SOCS-3 expression measured. SOCS-3 protein levels in VAN were measured by Western blot following leptin administration in vivo. Leptin resulted in appearance of pSTAT3 in VAN of low-fat-fed rats and rats resistant to diet-induced obesity but not diet-induced obese (DIO) rats. However, leptin signaling was normal in arcuate neurons. SOCS-3 expression was increased in VAN of DIO rats. In cultured VAN, LPS increased SOCS-3 expression and inhibited leptin-induced pSTAT3 in vivo. We conclude that VAN of diet-induced obese rats become leptin resistant; LPS and SOCS-3 may play a role in the development of leptin resistance.lipopolysaccharide; high-fat diet; suppressor of cytokine signaling-3 THE GUT PLAYS A CRUCIAL ROLE in sensing luminal contents that is important for the efficient digestion and absorption of ingested nutrients but also in integration of other physiological processes that regulate metabolism and energy expenditure, such as pancreatic ␤-cell function, hepatic function, and also food intake (34). In response to the presence or absence of food, enteroendocrine cells of the gut release anorexic or orexigenic hormones, respectively. The first site of integration of these signals occurs at the level of vagal afferent neurons (VAN), which project to and stimulate second-order neurons in the dorsal vagal complex of the hindbrain (27). VAN express receptors for many of the anorexigenic and orexigenic hormones released from the gut wall and mediate changes in gastrointestinal function and food intake in response to luminal nutrients (18).Leptin is a gut and adipose tissue-derived hormone that regulates a range of biological functions and processes, including energy intake and expenditure, body fat, neuroendocrine systems...

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Cholecystokinin Regulates Expression of Y2 Receptors in Vagal Afferent Neurons Serving the Stomach

Cited by 79 publications

References 44 publications

Anatomical and histological profiling of orphan G-protein-coupled receptor expression in gastrointestinal tract of C57BL/6J mice

Anatomical and histological profiling of orphan G-protein-coupled receptor expression in gastrointestinal tract of C57BL/6J mice

Expression of transient receptor potential channels and two-pore potassium channels in subtypes of vagal afferent neurons in rat

Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons

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