Activation of Muscarinic Acetylcholine Receptor Subtype 4 Is Essential for Cholinergic Stimulation of Gastric Acid Secretion: Relation to D Cell/Somatostatin

Takeuchi, Koji; Endoh, Takuya; Hayashi, Satoru; Aihara, Takeshi

doi:10.3389/fphar.2016.00278

Cited by 14 publications

(15 citation statements)

References 28 publications

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“…Seto et al have reported that acotiamide suppressed the gene expression of neuromedin U, a known stress‐related neuropeptide. Acotimaide and drugs with anticholinesterase activity have also reported to stimulate duodenal bicarbonate secretion in rat models . Considering previous studies and our data, acotiamide may act directly on the gut and also indirectly through the brain‐gut axis such as ghrelin in the central nervous system …”

Section: Introductionsupporting

confidence: 71%

Acotiamide attenuates central urocortin 2‐induced intestinal inflammatory responses, and urocortin 2 treatment reduces TNF‐α productions in LPS‐stimulated macrophage cell lines

Yanagawa

Futagami

Sakasegawa

et al. 2020

Neurogastroenterology Motil

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Background To determine whether central and in vitro administration of urocortin 2 (Ucn 2) affected intestinal inflammatory responses in LPS‐stimulated rat models and macrophage cell lines and acotiamide modified mucosal inflammation in this model. Methods Rats were divided into four groups. LPS‐stimulated group (n = 4); LPS‐ and urocortin 2‐treated group (n = 4); LPS‐ and acotiamide‐treated group (n = 4); and LPS‐, urocortin 2‐, and acotiamide‐treated group (n = 4). CD68‐, CCR2‐, and corticotropin‐releasing hormone receptor type 2 (CRHR2)‐positive cells were assessed by immunostaining. Myeloperoxidase (MPO) activity was measured. TNF‐α, IL‐6, and IL‐4 levels were measured by ELISA method. Gastric emptying and small intestinal transit time were determined using Evans blue. Key Results Central administration of Ucn 2 significantly aggravated infiltrations of CD68‐ and CCR2‐positive cells in the intestinal mucosa of LPS‐stimulated rat models compared to those in LPS treatment alone. Interestingly, acotiamide treatment significantly reduced the migrations of both CD68‐ and CCR2‐positive cells in the jejunum of central Ucn 2‐treated LPS‐stimulated rat models. Acotiamide significantly reduced the expression levels of IkB‐α phosphorylation in LPS‐ and MCP‐1‐stimulated NR8383 cells. Central administration of Ucn 2 significantly delayed gastric emptying. In contrast, Ucn 2 stimulation significantly reduced TNF‐α and IL‐6 productions in LPS‐stimulated NR8383 cells and astressin B reversed the inhibition of TNF‐α production in stimulated NR8383 cells. Acotiamide (30 μmol/L) significantly reduced TNF‐α and IL‐6 productions in LPS‐ and MCP‐1‐stimulated NR8383 cells. Conclusions and Inferences Central and in vitro treatments of Ucn 2 affected intestinal inflammatory responses, respectively, and acotiamide improved them.

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Section: Introductionsupporting

confidence: 71%

Acotiamide attenuates central urocortin 2‐induced intestinal inflammatory responses, and urocortin 2 treatment reduces TNF‐α productions in LPS‐stimulated macrophage cell lines

Yanagawa

Futagami

Sakasegawa

et al. 2020

Neurogastroenterology Motil

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“…To verify the physiological effect of the activation of sympathetic nervous system, which involves cholinergic receptors in salivary glands, SMG cells were stimulated with carbamylcholine chloride (carbachol) to increase the intracellular Ca 2+ . Stimulation of muscarinic receptor by carbachol enhances HCO 3 − secretion ( Takeuchi et al, 2015 ). The acute administration of carbachol induced a transient increase in the intracellular Ca 2+ level ( Figure 3A ).…”

Section: Resultsmentioning

confidence: 99%

Chloride Influx of Anion Exchanger 2 Was Modulated by Calcium-Dependent Spinophilin in Submandibular Glands

Lee

Shin

et al. 2018

Front. Physiol.

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Secretory glands including salivary glands by many hormonal inputs produce and secrete biological fluids determined by variety of ion transporters. Spinophilin is a multifunctional scaffolding protein, which involved in receptor signaling and regulation of anion exchangers AE2 activity. We found that spinophilin expressed in salivary glands. The role of salivary spinophilin on the modulation of chloride/bicarbonate exchange remains unknown. The spinophilin enhanced AE2 activity and associated with a STE20/SPS1-related kinase and showed an additive effect on the modulation of the activity of AE2. The cholinergic stimulation and subsequent intracellular Ca2+ increase was required for the interaction with AE2 and spinophilin and abrogated the enhanced effect of spinophilin on Cl− transporting activity. Ductal chloride/bicarbonate exchange activity was increased in pretreatment with carbachol. The CaMKII inhibitor KN-93 suppressed the chloride/bicarbonate exchange activity of ducts, suggesting that CaMKII was required for ductal chloride/bicarbonate exchange activity. Additionally, microtubule destabilization by nocodazole attenuated the interaction of AE2 and spinophilin and almost abolished the ductal chloride/bicarbonate exchange activity. The treatment of siRNA-spinophilin on the isolated salivary ducts also reduced the ductal chloride/bicarbonate exchange activity. Therefore, role of salivary spinophilin on AE2 may facilitate the Cl− influx from basolateral in salivary glands in response to cholinergic inputs.

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“…[8] Recently, it has been shown that the activation of M4 receptors found on D cells (responsible for somatostatin secretion) can indirectly enhance gastric acid secretion by inhibiting the release of somatostatin. [9] Gastrin is the main hormonal regulator of gastric acid secretion. It is secreted by G cells of the stomach that are localized to the antrum.…”

Section: Physiology Of Gastric Acid Secretionmentioning

confidence: 99%

“…The parasympathetic nervous system decreases the release of somatostatin from D cells. [9] Other substances that can either stimulate (gastrin-releasing peptide (GRP), ghrelin) or inhibit (ghrelin, secretin, cholecystokinin (CCK), and leptin) gastric acid secretion have also been described in the literature (Fig. 1).…”

Section: Physiology Of Gastric Acid Secretionmentioning

confidence: 99%

The Gastric and Intestinal Microbiome: Role of Proton Pump Inhibitors

Minalyan

Gabrielyan

Scott

et al. 2017

Curr Gastroenterol Rep

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Purpose of review The discovery of Helicobacter pylori and other organisms colonizing the stomach and the intestines has shed some light on the importance of microbiome in maintaining overall health and developing pathological conditions when alterations in biodiversity are present. The gastric acidity plays a crucial role in filtering out bacteria and preventing development of enteric infections. In this article, we discuss the physiology of gastric acid secretion and bacterial contribution to the composition of gastric and intestinal barriers and review the current literature on the role of proton pump inhibitors (PPIs) in the microbial biodiversity of the gastrointestinal tract. Recent findings Culture-independent techniques, such as 16S rRNA sequencing, have revolutionized our understanding of the microbial biodiversity in the gastrointestinal tract. Luminal and mucosa-associated microbial populations are not identical. Streptococcus is overrepresented in the biopsies of patients with antral gastritis and may also be responsible for the development of peptic ulcer disease. The use of PPIs favors relative streptococcal abundance irrespective of H. pylori status and may explain the persistence of dyspeptic symptoms in patients on PPI therapy. Increased risk of enteric infections has also been seen in patients taking PPIs. The overuse of PPIs leads to significant shift of the gastrointestinal microbiome towards a less healthy state. Summary With the advent of PPIs, many studies have demonstrated the significant changes in the microbial composition of both gastric and intestinal microbiota. Although they are considered relatively safe over-the-counter medications, PPIs in many cases are over- and even inappropriately used. Future studies assessing the safety of PPIs and their role in the development of microbiome changes should be encouraged.

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Activation of Muscarinic Acetylcholine Receptor Subtype 4 Is Essential for Cholinergic Stimulation of Gastric Acid Secretion: Relation to D Cell/Somatostatin

Cited by 14 publications

References 28 publications

Acotiamide attenuates central urocortin 2‐induced intestinal inflammatory responses, and urocortin 2 treatment reduces TNF‐α productions in LPS‐stimulated macrophage cell lines

Acotiamide attenuates central urocortin 2‐induced intestinal inflammatory responses, and urocortin 2 treatment reduces TNF‐α productions in LPS‐stimulated macrophage cell lines

Chloride Influx of Anion Exchanger 2 Was Modulated by Calcium-Dependent Spinophilin in Submandibular Glands

The Gastric and Intestinal Microbiome: Role of Proton Pump Inhibitors

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