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

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.