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

Cai YL, Zhang MH, Huang X, Jiang JZ, Piao LH, Jin Z, Xu WX - Gastroenterol Res Pract (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Yanbian University School of Medicine, 977 Gongyuan Road, Yanji, Jilin 133002, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Effect of CNP on intracellular cGMP and cAMP levels in gastric smooth muscle of diabetic and control rats. (a) CNP increased intracellular cGMP level in gastric smooth muscle, which was more significant in the diabetic rats than in controls (n = 8, #P < 0.01 versus vehicle, *P < 0.01 versus control). (b) CNP increased intracellular cAMP level in gastric smooth muscle, which was more significant in the diabetic rats than in controls (n = 8, #P < 0.01 versus vehicle, *P < 0.01 versus control).
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fig2: Effect of CNP on intracellular cGMP and cAMP levels in gastric smooth muscle of diabetic and control rats. (a) CNP increased intracellular cGMP level in gastric smooth muscle, which was more significant in the diabetic rats than in controls (n = 8, #P < 0.01 versus vehicle, *P < 0.01 versus control). (b) CNP increased intracellular cAMP level in gastric smooth muscle, which was more significant in the diabetic rats than in controls (n = 8, #P < 0.01 versus vehicle, *P < 0.01 versus control).

Mentions: CNP binds to the NPR-A or NPR-B in smooth muscle cell membrane and causes the production of cGMP by activating pGC. Since the inhibitory effect of CNP on spontaneous contraction was potentiated in diabetic rats, in succession, the effects of CNP on cGMP and cAMP generations were observed. Our experiments demonstrated that CNP significantly increased intracellular cGMP and cAMP concentrations in the gastric smooth muscles of both control and diabetic rats. cGMP and cAMP productions in control rats were increased from 0.71 ± 0.09 pmol/μL and 0.15 ± 0.05 pmol/μL before to 1.37 ± 0.12 pmol/μL and 0.23 ± 0.03 pmol/μL after the administration of CNP, respectively, and the increase percentage was 93.78% and 56.16%, respectively (Figures 2(a) and 2(b), n = 8, P < 0.01), while, in the diabetic group, the cGMP and cAMP productions were increased from 0.83 ± 0.22 pmol/μL and 0.17 ± 0.05 pmol/μL before to 2.15 ± 0.16 pmol/μL and 0.37 ± 0.07 pmol/μL after the administration of CNP, respectively, and the increase percentage was 159% and 118%, respectively (Figures 2(a) and 2(b), n = 8, P < 0.01). The CNP-induced productions of cGMP and cAMP in gastric smooth muscle were significantly potentiated in diabetic rats.


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

Cai YL, Zhang MH, Huang X, Jiang JZ, Piao LH, Jin Z, Xu WX - Gastroenterol Res Pract (2015)

Effect of CNP on intracellular cGMP and cAMP levels in gastric smooth muscle of diabetic and control rats. (a) CNP increased intracellular cGMP level in gastric smooth muscle, which was more significant in the diabetic rats than in controls (n = 8, #P < 0.01 versus vehicle, *P < 0.01 versus control). (b) CNP increased intracellular cAMP level in gastric smooth muscle, which was more significant in the diabetic rats than in controls (n = 8, #P < 0.01 versus vehicle, *P < 0.01 versus control).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4390109&req=5

fig2: Effect of CNP on intracellular cGMP and cAMP levels in gastric smooth muscle of diabetic and control rats. (a) CNP increased intracellular cGMP level in gastric smooth muscle, which was more significant in the diabetic rats than in controls (n = 8, #P < 0.01 versus vehicle, *P < 0.01 versus control). (b) CNP increased intracellular cAMP level in gastric smooth muscle, which was more significant in the diabetic rats than in controls (n = 8, #P < 0.01 versus vehicle, *P < 0.01 versus control).
Mentions: CNP binds to the NPR-A or NPR-B in smooth muscle cell membrane and causes the production of cGMP by activating pGC. Since the inhibitory effect of CNP on spontaneous contraction was potentiated in diabetic rats, in succession, the effects of CNP on cGMP and cAMP generations were observed. Our experiments demonstrated that CNP significantly increased intracellular cGMP and cAMP concentrations in the gastric smooth muscles of both control and diabetic rats. cGMP and cAMP productions in control rats were increased from 0.71 ± 0.09 pmol/μL and 0.15 ± 0.05 pmol/μL before to 1.37 ± 0.12 pmol/μL and 0.23 ± 0.03 pmol/μL after the administration of CNP, respectively, and the increase percentage was 93.78% and 56.16%, respectively (Figures 2(a) and 2(b), n = 8, P < 0.01), while, in the diabetic group, the cGMP and cAMP productions were increased from 0.83 ± 0.22 pmol/μL and 0.17 ± 0.05 pmol/μL before to 2.15 ± 0.16 pmol/μL and 0.37 ± 0.07 pmol/μL after the administration of CNP, respectively, and the increase percentage was 159% and 118%, respectively (Figures 2(a) and 2(b), n = 8, P < 0.01). The CNP-induced productions of cGMP and cAMP in gastric smooth muscle were significantly potentiated in diabetic rats.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Yanbian University School of Medicine, 977 Gongyuan Road, Yanji, Jilin 133002, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus