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...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.展开更多
基金supported by the National Natural Science Foundation of China(No.30470642 and No.30670780)Shandong Province Tackle Key Problems in Science and Technology Program( No.2008GG10002006 )+1 种基金Shandong Province Health Department ( No.2007HZ026)Qingdao Municipal Science and Technology Commission (No.05-1-JC-93)
文摘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.
