Involvement of interstitial cells of Cajal in nicotinic acetylcholine receptor-induced relaxation of the porcine lower esophageal sphincter

Otsuka, Yoshihiro; Bai, Xiaopeng; Tanaka, Yoshimasa; Ihara, Eikichi; Chinen, Takatoshi; Ogino, Hitoshi; Ogawa, Yoshihiro

doi:10.1016/j.ejphar.2021.174491

Cited by 4 publications

(4 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, Li et al (15) suggested that cisplatin treatment reduces acetylcholine (ACh) concentration and decreases the expression of its receptor, as well as the ACh activity in the gastric tissue, inducing damage to the Interstitial cells of Cajal (ICCs) and affecting GE. Thus, ICCs play a fundamental role in GI function associated with neurotransmitters involved in controlling GI contractility (16). As ATP may act as a neurotransmitter for inhibitory enteric neurons, which stimulate ICCs (17), this could explain the reversal of GE found in this research.…”

Section: Discussionmentioning

confidence: 65%

Moderate physical exercise and ATP modulate the P2X7 receptor and improve cisplatin-induced gastric emptying delay in rats

Gomes,

Santos,

Pinheiro

et al. 2024

Braz J Med Biol Res

View full text Add to dashboard Cite

Patients undergoing chemotherapy with cisplatin commonly present gastrointestinal effects such as constipation and gastric emptying (GE) delay. Both the purinergic system and physical exercise modulate the gastrointestinal (GI) tract. In the current study, we investigated the role of ATP, physical exercise, and P2X7 receptor blocking on GE delay induced by cisplatin in rats. Male rats were divided into the following groups: control (C), cisplatin (Cis), exercise (Ex), Brilliant Blue G (BBG), ATP, Cis+Ex, Cis+ATP, Cis+BBG, Cis+Ex+BBG, Cis+Ex+BBG+ATP, and Cis+ATP+BBG. GE delay was induced by treatment with 1 mg/kg cisplatin (1 time/week for 5 weeks, ip). The moderate physical exercise was swimming (1 h/day, 5 days/week for 5 weeks). At the end of the treatment or exercise and 30 min before the GE assessment, some groups received BBG (50 mg/kg, sc) or ATP (2 mg/kg, sc). Then, GE was assessed after a 10-min postprandial period. Chronic use of Cis decreased GE delay (Po0.05) compared to the control group. Both exercise and ATP prevented (Po0.05) GE delay compared to Cis. The pretreatment with BBG significantly inhibited (Po0.05) the effect of exercise and ATP. On the other hand, the association between exercise and ATP reversed (Po0.05) the effect of the BBG and prevented GE delay. Therefore, we suggest that both exercise and treatment with ATP activate P2X7 receptors and prevent GE delay induced by cisplatin in rats.

show abstract

Section: Discussionmentioning

confidence: 65%

Moderate physical exercise and ATP modulate the P2X7 receptor and improve cisplatin-induced gastric emptying delay in rats

Gomes,

Santos,

Pinheiro

et al. 2024

Braz J Med Biol Res

View full text Add to dashboard Cite

show abstract

“…However, it should be noted that P2Y receptors might be located on interstitial cells of Cajal (ICCs). This is because Otsuka et al reported that ATP might stimulate the ICCs via P2 receptors and then induce relaxation of smooth muscle of the lower esophageal sphincter [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Purinergic inhibitory regulation of esophageal smooth muscle is mediated by P2Y receptors and ATP-dependent potassium channels in rats

Shiina,

Suzuki,

Horii

et al. 2024

J Physiol Sci

View full text Add to dashboard Cite

Purines such as ATP are regulatory transmitters in motility of the gastrointestinal tract. The aims of this study were to propose functional roles of purinergic regulation of esophageal motility. An isolated segment of the rat esophagus was placed in an organ bath, and mechanical responses were recorded using a force transducer. Exogenous application of ATP (10–100 μM) evoked relaxation of the esophageal smooth muscle in a longitudinal direction under the condition of carbachol (1 μM) -induced precontraction. Pretreatment with a non-selective P2 receptor antagonist, suramin (500 μM), and a P2Y receptor antagonist, cibacron blue F3GA (200 μM), inhibited the ATP (100 μM) -induced relaxation, but a P2X receptor antagonist, pyridoxal phosphate-6-azophenyl-2,4-disulfonic acid (50 μM), did not affect it. A blocker of ATP-dependent potassium channels (KATP channels), glibenclamide (200 μM), inhibited the ATP-induced relaxation and application of an opener of KATP channels, nicorandil (50 μM), produced relaxation. The findings suggest that ATP is involved in inhibitory regulation of the longitudinal smooth muscle in the muscularis mucosae of the rat esophagus via activation of P2Y receptors and then opening of KATP channels.

show abstract

“…nAChR is a nicotine‐dependent receptor, and its expression level plays an important role in the development of smoking‐related diseases, especially respiratory diseases, 9 such as chronic obstructive pulmonary disease (COPD) and lung cancer. Genome‐wide association studies have shown that CHRNA5 gene (encoding α5‐nAChRs [α5‐nAChR]) polymorphisms are significantly related to the occurrence and development of cancer, especially lung cancer 10,11 ; it is highly expressed in esophageal cancer, gastric cancer and lung cancer and plays an important role in tumor cell proliferation, invasion and metastasis 12 . Our previous studies have shown that α5‐nAChR mediates the development and progression of nicotine‐induced lung cancer, activates Hif‐1α/VEGF, JAK2/STAT3, and Jab/Csn5 signaling, and promotes the proliferation and migration of lung cancer cells 13–15 .…”

Section: Introductionmentioning

confidence: 99%

“…Genome-wide association studies have shown that CHRNA5 gene (encoding α5-nAChRs [α5-nAChR]) polymorphisms are significantly related to the occurrence and development of cancer, especially lung cancer 10,11 ; it is highly expressed in esophageal cancer, gastric cancer and lung cancer and plays an important role in tumor cell proliferation, invasion and metastasis. 12 Our previous studies have shown that α5-nAChR mediates the development and progression of nicotine-induced lung cancer, activates Hif-1α/VEGF, JAK2/STAT3, and Jab/Csn5 signaling, and promotes the proliferation and migration of lung cancer cells. [13][14][15] However, the underlying molecular mechanisms are not yet well characterized.…”

mentioning

confidence: 96%

PLEK2 mediates metastasis and invasion via α5‐nAChR activation in nicotine‐induced lung adenocarcinoma

Li,

Wang

et al. 2023

Molecular Carcinogenesis

View full text Add to dashboard Cite

Evidence has shown a strong relationship between smoking and epithelial mesenchymal transition (EMT). α5‐nicotinic acetylcholine receptor (α5‐nAChR) contributes to nicotine‐induced lung cancer cell EMT. The cytoskeleton‐associated protein PLEK2 is mainly involved in cytoskeletal protein recombination and cell stretch migration regulation, which is closely related to EMT. However, little is known about the link between nicotine/α5‐nAChR and PLEK2 in lung adenocarcinoma (LUAD). Here, we identified a link between α5‐nAChR and PLEK2 in LUAD. α5‐nAChR expression was correlated with PLEK2 expression, smoking status and lower survival in vivo. α5‐nAChR mediated nicotine‐induced PLEK2 expression via STAT3. α5‐nAChR/PLEK2 signaling is involved in LUAD cell migration, invasion and stemness. Moreover, PLEK2 was found to interact with CFL1 in nicotine‐induced EMT in LUAD cells. Furthermore, the functional link among α5‐nAChR, PLEK2 and CFL1 was confirmed in mouse xenograft tissues and human LUAD tissues. These findings reveal a novel α5‐nAChR/PLEK2/CFL1 pathway involved in nicotine‐induced LUAD progression.

show abstract

Involvement of interstitial cells of Cajal in nicotinic acetylcholine receptor-induced relaxation of the porcine lower esophageal sphincter

Cited by 4 publications

References 47 publications

Moderate physical exercise and ATP modulate the P2X7 receptor and improve cisplatin-induced gastric emptying delay in rats

Moderate physical exercise and ATP modulate the P2X7 receptor and improve cisplatin-induced gastric emptying delay in rats

Purinergic inhibitory regulation of esophageal smooth muscle is mediated by P2Y receptors and ATP-dependent potassium channels in rats

PLEK2 mediates metastasis and invasion via α5‐nAChR activation in nicotine‐induced lung adenocarcinoma

Contact Info

Product

Resources

About