Effect Of Interstitial Cells Of Cajal On Intestinal Tract Smooth Constration Induced By Motilin Receptor Agonist ABT-229

Background and ObjectiveErythromycin (EM) is a kind of macrolide antibiotic, in recent years it was found has effect of motilin-like, is a kind of motilin receptor agonist. Erythromycin has a good effect on our pediatric gastrointestinal disease such as: neonatal feeding intolerance, gastroesophageal reflux, but it is not widely used, because of its broad-spectrum antimicrobial effect, long-term application may lead to bacterial disorder. Erythromycin derivative is a kind of chemical substances to get rid of its antimicrobial activity, several have been developed so far, including: ABT-229 (Abbott, USA) , GM-523, GM-574, GM-611 (Japan) and so on, has a strong role in promoting gastrointestinal motility, gastrointestinal motility agents, as there will be a bright future. Interstitial cell of cajal ( ICC) is a kind of special cells in the gastrointestinal tract,【33】which was considered to be pacemaker cells in the human gastrointestinal tract , ICC reduction in the number and distribution of abnormalities, ICC network deficits was found in about 2 / 3 of patients with functional dyspepsia and slow conduction. Erythromycin and its derivatives on the role of agonist for ICC is unclear, so the study for the role of ICC during motilin receptor agonists to promote gastrointestinal motility is very necessary,【34】and application of drug to intervention ICC on impaired gastrointestinal motility specificly seems to a promising target【35】. Therefore ,this study set intestinal smooth muscle in rabbits and rats as the target , To investigate the role of interstitial cells of Cajal (ICC) in construction of intestinal tract smooth muscle induced by motilin receptor agonist(ABT-229), provide more experimental argument in study the mechanism of ICC. To investigate the role of interstitial cells of Cajal (ICC) in construction of intestinal tract smooth muscle induced by motilin receptor agonist.MethodsPart one :Two kinds of smooth muscle segments were isolated from the duodenum and colon of rabbit. Both kinds of smooth muscle were divided into two groups :group a (normal ICC group of duodenum); group c (lesion ICC group of duodenum); group b (normal ICC group of colon); group d (lesion ICC group of colon) ,each group contain 20 segments .We selective destroyed ICC in the smooth muscle specificity by methylene blue plus light. Then contrast the frequency and amplitude of group a and c ,group b and d ; Then motilin receptor agonist (ABT-229) were added into the Krebs solution, the frequency and amplitude of smooth muscle before and after added were recorded and compared.Part two: The smooth muscle segments were isolated from the colon of Rat. Then contrast the frequency and amplitude before and after motilin receptor agonist (ABT-229) were added into the Krebs solution, the frequency and amplitude of smooth muscle before and after added were recorded and compared.Results1. The electron microscope demonstrate: ICC in methylene blue plus light group were destruction ; the smooth muscle cells and neuron scattered close to ICC were normal .In group a , the construction frequency were(17.89±1.88)vic/min ,compare with the after ABT-229 were added(18.76±1.18)vic/min, there had no significant difference (P>0.05); the amplitude of group a were (343±28)mg , the amplitude were lower compare with after ABT-229 added [(597±68)mg](P<0.001) ; In group b ,the frequency were (5.89±1.03)vic/min , the amplitude were (724±85)mg ,after ABT-229 added , the construction frequency were increased to(8.45±0.69)vic/min(P<0.001),and the amplitude were (897±89)mg(P<0.05), which was not affected by pretreatment with TTX , however it can be weaken by Nifedipine significantly . In group c and d ,the rhythmic contraction was disappear almost : In group c the construction frequency were (1.06±0.24)vic/min, and the amplitude were (50±10)mg ; In group d ,the construction frequency were (0.71±0.10) vic/min ,and the amplitude were (45±10)mg , compared with the normal group the amplitude and frequency decreased ,which had significant difference (P<0.001); then ABT-229 were added, In group c ,the construction frequency were (1.17±0.25) vic/min , the amplitude were (58±11)mg; In group d, the construction frequency were (0.78±0.11) vic/min , the amplitude were (57±8)mg , there had no significant difference in amplitude and frequency between before and after ABT-229 added(P>0.05). After Ach (100μmol /L) were added, both group c and d can generate construction obviously.2. After 1h incubation Rat colonic smooth muscle strips contraction become stable: contraction frequency and amplitude were (2.80±0.49) times / min and (575±87) mg. ABT-229 were added , the contraction frequency and amplitude were (2.96±0.52) times / min, (580±84) mg, there had no significant difference in amplitude and frequency between before and after ABT-229 added(P>0.05).Conclusions1. ICC play an important role in the rhythmic contraction of intestinal tract ;2. The promotion of motilin receptor agonist to intestinal tract were mediated by ICC ;3. human can emerge gastrointestinal tract motivation functional impairment in the same way ;4. when the number of ICC absence to a certain extent or the network of ICC were incomplete ,the medication maybe have not a good effection .5. Motilin receptor agonist ABT-229 has a promoting effect on the contraction of rabbit colonic muscle in a dose dependent way , whereas has no such effect in rat colon smooth; we could take a speculated that there maybe not exist motilin receptor in rat colon muscle;6. In experimental such a study of gastrointestinal motility, the animals has similar structure and function of the human gastrointestinal tract such as rabbit should be chosen.