Motilin Effects And Mechanism Of The Hormone On The Guinea Pig Gastric Smooth Muscle Contraction And Relaxation Activities

Objective:This study investigates the gastroprokinetic effects of motilin and erythromycin(EM-A) and its potential mechanism in guinea pigs(Cavia porcellus) in vitro.Methods:Guinea pig stomach strips were mounted under organ baths containing Krebs solution.Motilin,EM-A,Nω-Nitro-L-arginine(L-NNA),sodium nitroprusside(SNP) or 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,SNP and L-AA in the gastric anturm and fundus of guinea pigs.In addition,we observed the expression of motilin receptors and nNOS in the gastric myenteric plexus of guinea pigs by fluo-immunohistochemistry.Results: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 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 off-contraction and on-relaxation that was reversed into a cholinergically mediated contraction by addition of the nitric oxide synthase(NOS) inhibitors L-NNA.The effects of motilin on strip responses were significantly enhanced compared with EM-A.However,in the antral strips,motilin and EM-A only increased off-contractions.The response to motilin and EM-A in the presence of SNP or L-AA did differ from that obtained with motilin or EM-A alone.It showed that both SNP and L-AA could enhance on-relaxations and reduce off-contractions induced by motilin and EM-A.Motilin receptor and nNOS immunoreactive positive neurons were expressed in the gastric myenteric plexus of the guinea pigs.Conclusion:The on-relaxations were non-adrenergic,non-cholinergic(NANC) mediated and the off-contractions can cholinergically mediated.Both motilin and EM-A can increase relaxations in the fundic strips and increase contractions in the antral strips and that this effect is mediated by activating gastric nervous and NO pathways.