Comparative study in the effect of C-type natriuretic peptide on gastric motility in various animals

To investigate the effect of natriuretic peptides on gastric motility in various animals, and the effect of C-type natriuretic peptide (CNP) on spontaneous contraction of gastric smooth muscle in rat, guinea-pig and human in vitro was compared.

Spontaneous contraction of gastric smooth muscle was recorded by four channel physiograph.

In the guinea-pig and rat gastric antral circular smooth muscle, CNP markedly decreased the amplitude of spontaneous contraction but it didn't affect the frequency, however, the contractile activity was completely inhibited by CNP in gastric antral longitudinal smooth muscle. In the human gastric antral circular and longitudinal smooth musle, CNP completely inhibited spontaneous contraction. In the circular smooth muscle of guinea-pig and rat gastric fundus, CNP obviously decreased the amplitude of spontaneous contraction but it didn't affect the frequency, however, the contractile activity was completely inhibited by CNP in smooth muscle of fundus longitudinal. In the circular and longitudinal smooth muscle of guinea-pig gastric body, CNP at first induced a relaxation and then an increase in amplitude of spontaneous contraction (rebound contraction), but the frequency was not changed. After the circular smooth muscle of gastric body was pretreated with atropine, an M receptor blocker, the rebound contraction was abolished; In circular and longitudinal smooth muscle of rat gastric body, CNP induced a transient and slight relaxation and successively followed by the recovery in amplitude of spontaneous contraction but it also didn't affect the frequency. After the smooth muscle was pretreated with atropine, the transient and slight relaxation was replaced by long term and complete inhibition; The percentage of CNP-induced inhibition was 76.77+/-6.21 % (fundus), 67.21+/-5.32 % (body) and 58.23+/- 6.21 % (antral) in the gastric circular muscle, however, the inhibitory percentage was 100+/-0.00 % (fundus), 68.66+/- 3.55 % (body) and 100+/-0.00 % (antrum) in the gastric longitudinal smooth muscle of guinea-pigs; In the rat, the percentage of CNP-induced inhibition was 95.87+/-4.12 % (fundus), 94.91+/-5.08 % (body) and 66.32+/-7.32 % (antrum)in the gastric circular smooth muscle, but in the longitudinal smooth muscle, CNP completely inhibited the spontaneous contraction. Using LY83583, a guanylate cyclase inhibitor, and zaparinast as a phosphoesterase inhibitor to inhibit the generation of cGMP, the effect of CNP on the spontaneous contraction was markedly weakened by LY83583, however, the inhibitory effect was enhanced by zaparinast.

(1) CNP can obviously inhibit the spontaneous contraction of gastric antral circular and longitudinal smooth muscle in the rat, guinea-pig and human. The order of inhibitory potency is human >rat> guinea-pig. (2) In the same animals, the inhibitory effect of CNP on spontaneous contraction is the most powerful in fundus and the weakest in antrum, in the same position, the inhibitory effect on the circular smooth muscle is more powerful than that on longitudinal smooth muscle. (3) The inhibitory effect of CNP on spontaneous contraction in the gastric smooth muscle is mediated by a cGMP dependent pathway.