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

Abstract

Abstract This study investigates the gastroprokinetic effects of motilin and erythromycin A (EM-A) and its potential mechanism in guinea pigs Cavia 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.