Of Ghrelin On The Guinea Pig Gastric Smooth Muscle Contraction And Relaxation Activities And Mechanism Study

Objective:To investigate and compare the influences of Ghrelin and growth hormone releasing peptide 6(GHRP-6) on the contractility of stomach smooth muscle in guinea pigs,and to study the related mechanism.Methods:The myenteric plexuses of gastric fundus and antrium in guinea pigs were stimulated with electrical field stimulation(EFS) to observe the influence of Ghrelin and GHRP-6 on the contractility of stomach smooth muscle.The influences of N-nitro-L-arginine(L-NNA) and L-Arginine(L-AA) on the effect of Ghrelin and GHRP-6 were studied to disclose the mechanism of the effects of Ghrelin and GHRP-6; On the hand we observed the synergistic effects of ghrelin and motilin on contractibility of guinea pig antral strips.The expression of ghrelin receptor in the gastric myenteric plexus was studied by fluo-immunohistochemistry assay.Results: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,ghrelin and GHRP-6 induced on-relaxation and off-contraction and both ghrelin and GHRP-6 may significantly reduced on-response and increased off-response.And the effects of ghrelin on strip responses were significantly enhanced compared with GHRP-6.The on-responses could be reversed 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 ghrelin or GHRP-6.In the antral strips,EFS only induces off-contractions which may be increased by both ghrelin and GHRP-6.Ghrelin and motilin have synergistic action in the antral strips.In the immunohistochemistry staining experiment,it shows that ghrelin receptor immunoreaction expressed in the gastric myenteric plexus of guinea pig.Conclusion:Both ghrelin and GHRP-6 can promote the contractility of stomach smooth muscle in guinea pigs through stimulating myenteric plexuses of gastric fundus and antrium,and this effect is possibly involves the NO pathway.