Published online Sep 15, 2003. doi: 10.3748/wjg.v9.i9.2054
Revised: May 23, 2003
Accepted: June 27, 2003
Published online: September 15, 2003
AIM: To investigate ion channel mechanism in CNP-induced relaxation of gastric circular smooth muscle in guinea pigs.
METHODS: Spontaneous contraction of gastric smooth muscle was recorded by a four-channel physiograph. The whole cell patch-clamp technique was used to record calcium-activated potassium currents and membrane potential in the gastric myocytes isolated by collagenase.
RESULTS: C-type natriuretic peptide (CNP) markedly inhibited the spontaneous contraction in a dose-dependent manner in gastric circular smooth muscle in guinea pigs. Ly83583, an inhibitor of guanylate cyclase, weakened CNP-induced inhibition on spontaneous contraction but Zaparinast, an inhibitor of cGMP sensitive phosphoesterase, potentiated CNP-induced inhibition in gastric circular smooth muscles. The inhibitory effects of CNP on spontaneous contraction were blocked by tetrathylammonium (TEA), a nonselective potassium channel blocker. C N P hyperpolarized membrane potential from -60.0 mV ± 2.0 mV to -68.3 mV ± 3.0 mV in a single gastric myocyte. CNP increased calcium-activated potassium currents (IK(ca)) in a dose-dependent manner in gastric circular myocytes. CNP also increased the spontaneously transient outward currents (STOCs). Ly83583 partly blocked CNP-induced increase of calcium-activated potassium currents, but Zaparinast potented the effect.
CONCLUSION: CNP inhibits spontaneous contraction, and potassium channel may be involved in the process in gastric circular smooth muscle of guinea pigs. CNP-induced increase of IK(ca) is mediated by a cGMP dependent pathway.