cGMP–PDE3–cAMP signal pathway involved in the inhibitory effect of CNP on gastric motility in rat

Cai, Yujun; Sun, Qian; Huang, Xu; Jiang, Jingzhi; Zhang, Mohan; Piao, Lihua; Zheng, Jin; Xu, Wen‐Xie

doi:10.1016/j.regpep.2012.11.001

Cited by 8 publications

(9 citation statements)

References 17 publications

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“…[17][18][19] There was a report which confirmed that inhibitory effect of CNP on gastric smooth muscle was strengthened in diabetic rat via up-regulation of cGMP, 20 are the most common isoforms in GI tract, and PDE3 is a main regulator of murine gastrointestinal circular muscle contraction, while higher concentration of PDE2 could partly influence the gut motility. 22,23 Cai et al 24 confirmed only the expression level of PDE3 was decreased in gastric smooth muscle of diabetic rats. There was no relevant report about the changes in PDEs in the colon of diabetic mice.…”

Section: Discussionmentioning

confidence: 94%

“…PDEs can specifically hydrolyze the cGMP within the cells and therefore have a key role in regulating the signal conveyed by cGMP. PDE3 and PDE2 are the most common isoforms in GI tract, and PDE3 is a main regulator of murine gastrointestinal circular muscle contraction, while higher concentration of PDE2 could partly influence the gut motility . Cai et al confirmed only the expression level of PDE3 was decreased in gastric smooth muscle of diabetic rats.…”

Section: Discussionmentioning

confidence: 99%

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Electroacupuncture promotes the gastrointestinal motility of diabetic mice by CNP/NPR‐B‐cGMP and PDE3A‐cGMP signaling

Song

et al. 2019

Neurogastroenterology Motil

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Background Electroacupuncture (EA) can promote gastrointestinal (GI) motility of diabetic mice, but the mechanism is not clearly elucidated. Natriuretic peptides (NPs) were related to the diabetes‐induced gut dysfunction of mice, which may be associated with ICC (interstitial cells of cajal). Besides, EA could increase the ICC of diabetic mice. Our aim was to explore whether EA can promote the gut motility by CNP/NPR‐B‐cGMP and PDE3A‐cGMP signaling in diabetic mice, and the relationship between NPs and ICC. Methods Wild C57BL/6 male mice were divided into five groups: control group, diabetic mellitus (DM group), diabetic mellitus plus sham EA group (SEA), diabetic mellitus plus low‐frequency EA group (LEA), and diabetic mellitus plus high‐frequency group (HEA). Gastrointestinal motility was assessed by gastric emptying and GI transit test. Immunofluorescence staining was applied to assess the expression level of CNP, NPR‐B, and c‐Kit. Western blot, PCR, and ELISA were used to detect the level of CNP, NPR‐B, PDE2A, PDE3A, c‐Kit, mSCF, and cGMP content. The correlativity between NPR‐B and mSCF was evaluated by Pearson's correlation and linear regression analyses. Key Results (a) EA could improve the GI dysfunction of diabetic mice. (b) CNP, NPR‐B, and cGMP contents were decreased, but the level of PDE3A, c‐Kit, and mSCF was increased in the EA groups. (c) There was a negative correlation between NPR‐B and mSCF among the groups. Conclusions and Inferences Electroacupuncture promotes the GI function by CNP/NPR‐B‐cGMP and PDE3A‐cGMP signaling in diabetic mice; up‐regulated mSCF/c‐Kit signaling by EA may be mediated partially via down‐regulation of CNP/NPR‐B signaling.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Electroacupuncture promotes the gastrointestinal motility of diabetic mice by CNP/NPR‐B‐cGMP and PDE3A‐cGMP signaling

Song

et al. 2019

Neurogastroenterology Motil

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“…35 For instance, GC-A-induced cGMP is degraded primarily by PDE2 while GC-B-induced cGMP is degraded by PED3. 36, 37 PDE1 is largely responsible for renal cGMP PDE activity, 11 suggesting that renal cGMP is produced through sGC activation and degraded by PDE1. Thus, GC-A-mediated cGMP may activate effectors, distinct from those activated by the NO/sGC axis in cystic kidneys.…”

Section: Discussionmentioning

confidence: 99%

B-type natriuretic peptide overexpression ameliorates hepatorenal fibrocystic disease in a rat model of polycystic kidney disease

Holditch

Schreiber

Harris

et al. 2017

Kidney International

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Polycystic kidney disease (PKD) involves progressive hepatorenal cyst expansion and fibrosis, frequently leading to end-stage renal disease. Increased vasopressin and cAMP signaling, dysregulated calcium homeostasis, and hypertension play major roles in PKD progression. The guanylyl cyclase A agonist, B-type natriuretic peptide (BNP), stimulates cGMP and shows anti-fibrotic, anti-hypertensive, and vasopressin-suppressive effects, potentially counteracting PKD pathogenesis. Here, we assessed the impacts of guanylyl cyclase A activation on PKD progression in a rat model of PKD. Sustained BNP production significantly reduced kidney weight, renal cystic indexes and fibrosis, in concert with suppressed hepatic cystogenesis in vivo. In vitro, BNP decreased cystic epithelial cell proliferation, suppressed fibrotic gene expression, and increased intracellular calcium. Together, our data demonstrate multifaceted effects of sustained activation of guanylyl cyclase A on polycystic kidney and liver disease. Thus, targeting the guanylyl cyclase A-cGMP axis may provide a novel therapeutic strategy for hepatorenal fibrocystic diseases.

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“…For example, cGMP can increase intracellular cAMP through the inhibition of PDE3 to enhance the cardiac muscle contractility [ 23 , 24 ]. And we also found that cAMP generation induced by CNP through cGMP-PDE3-cAMP signal pathway activated PKA signal pathway and subsequent inhibition of L-type calcium current to inhibit the gastric smooth muscle motility together with cGMP, while cGMP-PDE2-cAMP signal pathway was not involved in the process [ 20 ]. Nevertheless, whether cGMP-PDE-cAMP signal pathway is involved in the mechanism of diabetes-induced gastric motility disorder has not been studied so far.…”

Section: Discussionmentioning

confidence: 99%

“…We have found that both NPR-B expression in smooth muscle of gastric antrum and the activity of membrane-bound guanylate cyclase (pGC) were significantly increased in diabetic rats, which indicate the upregulation of CNP-NPR-B/pGC-cGMP signal pathway in diabetic gastric antrum [ 18 , 19 ]. And we also found that cGMP produced through CNP-NPR signal pathway induced the generation of cAMP via cGMP-PDE3-cAMP signal pathway followed by the activation of PKA resulting in the inhibition of L-type calcium current, which inhibited the spontaneous contraction of gastric smooth muscle together with cGMP [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

CNP-pGC-cGMP-PDE3-cAMP Signal Pathway Upregulated in Gastric Smooth Muscle of Diabetic Rats

Cai

Zhang

Huang

et al. 2015

Gastroenterology Research and Practice

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Our previous studies have shown that CNP-NPR-B/pGC-cGMP is upregulated in the diabetic rats. The present study was designed to determine whether the upregulation of CNP-NPR-B/pGC-cGMP signal pathway affects cGMP-PDE3-cAMP signal pathway in diabetic gastric smooth muscle. The gastric smooth muscle motility was observed by using isometric measurement. PDEs expressions in diabetic gastric smooth muscle tissue were observed by using immunohistochemistry, Western blotting, and RT-PCR methods. The results demonstrated that the inhibitory effect of CNP on the spontaneous contraction of gastric antral circular smooth muscle was potentiated in STZ-induced diabetic rat. CNP-induced increase of cGMP and cAMP was much higher in diabetic gastric smooth muscle tissue than in controls. The expression of PDE3 is downregulated while the levels of gene expression of PDE1, PDE2, PDE4, and PDE5 were not altered in the diabetic gastric smooth muscle tissue. The results suggest that the sensitivity of gastric smooth muscle to CNP is potentiated via activation of CNP-pGC-cGMP-PDE3-cAMP signal pathway in STZ-induced diabetic rats, which may be associated with diabetes-induced gastric motility disorder.

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cGMP–PDE3–cAMP signal pathway involved in the inhibitory effect of CNP on gastric motility in rat

Cited by 8 publications

References 17 publications

Electroacupuncture promotes the gastrointestinal motility of diabetic mice by CNP/NPR‐B‐cGMP and PDE3A‐cGMP signaling

Electroacupuncture promotes the gastrointestinal motility of diabetic mice by CNP/NPR‐B‐cGMP and PDE3A‐cGMP signaling

B-type natriuretic peptide overexpression ameliorates hepatorenal fibrocystic disease in a rat model of polycystic kidney disease

CNP-pGC-cGMP-PDE3-cAMP Signal Pathway Upregulated in Gastric Smooth Muscle of Diabetic Rats

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