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.
Highlights
Gastrointestinal motility disorders are common complications of diabetes, which can happen in all regions of the gastrointestinal tract
We found that cGMP produced through C-type natriuretic peptide (CNP)-natriuretic peptide receptors (NPRs) 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]
The results suggest that the inhibitory effect of CNP on spontaneous contraction is potentiated in diabetic rats
Summary
Gastrointestinal motility disorders are common complications of diabetes, which can happen in all regions of the gastrointestinal tract. Diabetic gastrointestinal motility disorders and gastric emptying delay significantly affect the pharmacokinetics of hypoglycemic and other drugs, resulting in absorption delay of these drugs and poor glycemic control. The NPs-NPR-A, B/pGC-cGMP signal pathway was found to be involved in the inhibitory effect of NPs on spontaneous contraction in gastric smooth muscle of guinea pig, rat, and human [5, 6]. Elevation of intracellular cAMP and cGMP has been associated with smooth muscle relaxation in several regions of the gastrointestinal tract, including the lower oesophageal sphincter, ileum, proximal colon, taenia coli, and internal anal sphincter [7,8,9,10,11,12,13]. PDE1, PDE2, and PDE3 can hydrolyze both cAMP and cGMP, whereas
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