Kim et al proved the presence of DNP-like immunore activity in the rat colon, and that the DNP-like molecule may control colonic motility as a local regulator. Up to now, there is little research exploring the relationship between DNP and gastric motility. In the author's previous study, they demonstrated that DNP inhibited gastric motility. However, the mechanism remains unclear.
A research article to be published on September 21, 2008 in the World Journal of Gastroenterology addresses this question. The research team led by Prof. Guo from Centralab of the first Affiliated Hospital of Dalian Medical University used the patch-clamp technique, a pharmacologic approach and radioimmunoassays to systematically investigate if the cGMP/cGMP-dependent protein kinase (PKG) signaling pathway may participate in DNP-induced relaxation of gastric circular smooth muscle.
Their results showed that DNP markedly enhanced cGMP levels in gastric antral smooth muscle tissue and in the perfusion medium. DNP induced relaxation in gastric antral circular smooth muscle, which was inhibited by KT5823, a cGMP-dependent PKG inhibitor. DNP increased IK(Ca). This effect was almost completely blocked by KT5823, and partially blocked by LY83583, an inhibitor of guanylate cyclase to change the production of cGMP. DNP also increased spontaneous transient outward currents (STOCs). The effect of DNP on STOCs was abolished in presence by KT5823, but not affected by KT-5720, a PKA-specific inhibitor. It is concluded that DNP activates IK(Ca) and relaxes guinea-pig gastric antral circular smooth muscle via the cGMP/PKG-dependent singling axis, instead of cAMP/PKA pathway.
This work succeeded in better understanding the mechanism how DNP regulates gastric motility. It showed for the fist time that DNP activates IK(Ca) and relaxes guinea-pig gastric antral circular smooth muscle via the cGMP/PKG-dependent singling axis instead of cAMP/PKA pathway.