Inhibitory effect of dendroaspis natriuretic peptide on spontaneous contraction in gastric antral circular smooth muscles of guinea pigs

Abstract

Aim: To determine whether the natriuretic peptide receptor (NPR) is present in the stomach of guinea pigs and to investigate the effect of dendroaspis natriuretic peptide (DNP) on the gastric motility of guinea pigs and its mechanism. Methods: The distribution of the NPR was analyzed by autoradioimmunography. The spontaneous contraction of gastric antral circular muscles of guinea pigs was recorded by a 4-channel physiograph. The whole cell patch-clamp technique was introduced to record calcium-activated potassium currents in the gastric myocytes isolated by collagenase. Results: The NPR existed in the gastric fundus, gastric body, and gastric antrum of guinea pigs, and its density was largest in the gastric antrum. DNP inhibited spontaneous contraction and exhibited a dose-dependent manner. The DNP-induced inhibition was diminished by LY83583 (a guanylate cyclase inhibitor) and was potentiated by zaprinast (a cGMP-sensitive phosphoesterase inhibitor). The inhibitory effect of DNP on spontaneous contraction was also inhibited by tetraethylammonium (a non-selective potassium channel blocker); 10 nmol/L DNP increased the calcium-activated potassium currents in the gastric circular myocytes of guinea pigs. Conclusion: The NPR is most common in the gastric antrum of guinea pigs. DNP significantly inhibits gastric motility in the gastric antrum of guinea pigs. The inhibitory effect occurs via a cGMP-dependent pathway, and a calcium-activated potassium channel may be also involved in the relaxation induced by DNP in gastric antral circular smooth muscles.

C-type natriuretic-peptide-potentiated relaxation response of gastric smooth muscle in streptozotocin-induced diabetic rats

“…NPs are also secreted from gastric mucosa [14][15][16] . Our previous study indicated that CNP relaxes gastric circular and longitudinal smooth muscles in human, rat and guinea-pig stomach, and that NPRs are distributed in rat gastric smooth muscle layer [17][18][19] . In smooth muscle, CNP activates its cognate NPR-B, which includes an intracellular pGC domain and catalyzes the synthesis of cGMP within the cytosol [20] .…”

Effects of Dendroaspis Natriuretic Peptide on Calcium-Activated Potassium Current and Its Mechanism

“…However, there is no report about the effect of DNP on Ca 2+ -activated K + channels, particularly in gastrointestinal SMCs. In a previous study [15], we found that DNP inhibits spontaneous contraction in gastric antral circular myocytes. In the present study, DNP significantly and dose-dependently increases I K(Ca) and STOCs in gastric antral circular SMCs (Fig.…”

“…Kim et al [10] have for the first time demonstrated that DNP is present in rat colon and can control colonic motility as a local regulator. We have found that NPs can also regulate gastric motility [11][12][13][14]. Our further study indicates that the regulatory effect of DNP on spontaneous contraction in gastric antral circular SMCs occurs via a cGMP-dependent pathway [15].…”

Dendroaspis natriuretic peptide relaxes gastric antral circular smooth muscle of guinea-pig through the cGMP/cGMP-dependent protein kinase pathway

“…Evolutionary studies [8] have suggested the presence of DNP-like immunoreactivity in rat colon, and the DNP-like molecule may control colonic motility as a local regulator. Interestingly, we found that DNP inhibits spontaneous contraction in gastric circular smooth muscle [9] . NPs are similar to nitric oxide (NO), which play important physiological functions by affecting the activity of cGMP and cAMP.…”