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

AIM: To study the sensitivity of gastric smooth muscle to C-type natriuretic peptide (CNP) in streptozotocin (STZ)-induced diabetic rats. METHODS: The spontaneous contraction of a gastric smooth muscle strip was recorded by using physiological methods in rats. The expressions of CNP and natriuretic peptide receptor-B (NPR-B) in gastric tissue were examined by using immunohistochemistry techniques in the diabetic rat. RESULTS: At 4 wk after injection of STZ and vehicle, the frequency of spontaneous contraction of gastric smooth muscle was significantly reduced in diabetic rats, and the frequency was decreased from 3.10 ± 0.14 cycle/min in controls to 2.23 ± 0.13 cycle/min (n = 8, P < 0.01). However, the amplitude of spontaneous contraction was not significant different from the normal rat. CNP significantly inhibited spontaneous contraction of gastric smooth muscle in normal and diabetic rats, but the inhibitory effect was significantly potentiated in the diabetic rats. The amplitudes of spontaneous contraction were suppressed by 75.15% ± 0.71% and 58.92% ± 1.32% while the frequencies were decreased by 53.33% ± 2.03% and 26.95% ± 2.82% in diabetic and normal rats, respectively (n = 8, P < 0.01). The expression of CNP in gastric tissue was not changed in diabetic rats, however the expression of NPR-B was significantly increased in diabetic rats, and the staining indexes of NPR-B were 30.67 ± 1.59 and 17.63 ± 1.49 in diabetic and normal rat, respectively (n = 8, P < 0.01).CONCLUSION: The results suggest that CNP induced an inhibitory effect on spontaneous contraction of gastric smooth muscle, potentiated in diabetic rat via up-regulation of the natriuretic peptides-NPR-B-particulate guanylyl cyclase-cyclic GMP signal pathway.

Effect of motilin on the contractility of gastric smooth muscle via NO pathway in guinea pigs

This study investigates the gastroprokinetic effects of motilin and erythromycin A （EM-A） and its potential mechanism in guinea pigs Carla porcellus in vitro. Guinea pig stomach strips were mounted under organ baths containing Krebs solution. Motilin, EM-A, Nω-Nitro-L-arginine （L-NNA）, L-arginine （L-AA） were added to the bathing solution in a non-cumulative way. Then the effects of motilin and EM-A was studied during electrical field stimulation （EFS） in the absence and presence of L-NNA and L-AA in the gastric anturm and fundus of guinea pigs. In addition, we observed the co-expression of motilin receptors and neuronal nitric oxide synthase （nNOS） in the gastric myenteric plexus of guinea pigs by fluo-immunohistochemistry. The results showed that the circular muscle tissues of the gastric fundus generated on-relaxations and off-contractions with the frequency of 1 - 16 Hz. The on-responses induced a relaxation, partially mediated by the release of nitric oxide （NO） because addition of L-NNA turned the relaxations into cholinergically mediated contractions. The off-contractions were also cholinergically mediated as they disappeared under non-adrenergic, non-cholinergic （NANC） conditions using atropine and guanethidine. In fundic strips, motilin and EM-A induced on-relaxation and off-contraction and both motilin （1 μmol/L） and EM-A （100 μmol/L） may significantly increased on-response and reduced off-response （P 〈 0.05）. And the effects of motilin on strip responses were significantly enhanced compared with EM-A. The on-responses could be reversed into a cholinergically mediated contraction by addition of NOS inhibitors L-NNA. In contrast, administration of substrate of NOS, L-AA, significantly increased on-relaxations and reduced cholinergic motor responses which were induced by motilin or EM-A. However D-arginine （D-AA） did not change the above response induced by motilin or EM-A. In the antral strips, motilin and EM-A only increased off-contractions. The response to motilin and EM-A in the presence of L-NNA did differ from that obtained with L-NNA alone. It showed that both motilin and EM- A could enhance off-contractions induced by L-NNA （P 〈 0.05）. Immunohistochemistry study showed that motilin receptor immunoreactive positive neurons were co-localized with nNOS positive neurons in the gastric myenteric plexus of the guinea pigs. These results suggested that motilin or EM-A modulates gastrointestinal motility which was mediated by activating gastric nervous and NO pathways in guinea pigs gastro-intestinal tract.