The Effects of Yangrong Runchangshu Mixture on c-Kit,SP and VIP in the Colon of Rats with Slow Tran-sit Constipation / 中国药房

OBJECTIVE:To study the effects of Yangrong runchangshu mixture on tyrosine kinase receptor protein CD117 (c-Kit),substance P(SP)and myenteric nerve plexus vasoactive intestinal peptide(VIP)in the colon interstitial cell of Cajal of rat with slow transit constipation(STC). METHODS:Morphine hydrochloride(2.5 mg/kg)was given sc once daily for 45 consecu-tive days to establish STC rat models. 120 rats were randomized into a normal control (isometric normal saline) group,a model (isometric normal saline)group,Maren pill(positive control,14.7 g/kg)group and Yangrong runchangshu mixture high-dose and low-dose [15 and 7.5 g(medicinal materials)/kg] groups. After successful establishment of the models,drugs were given ig once dai-ly for 10 consecutive days. Immunohistochemical method was employed for staining. The changes in the structure and c-Kit,SP and VIP expressions in rats’colonic tissues were observed under the light microscope. RESULTS:Compared to the normal control group,those in the model group demonstrated weaker expressions of c-Kit and SP and less positive cells in colon,stronger expres-sion of VIP and more positive cells,with statistical significances (P<0.01);cellular morphology became abnormal obviously. Compared to the model group,those in Maren pill group and Yangrong runchangshu mixture high-dose and low-dose groups showed stronger expressions of c-Kit,SP and more positive cells in colon,weaker expressions of VIP and less positive cells with statistical significances (P<0.05);cellular morphology was improved to some extent. CONCLUSIONS:Yangrong runchangshu mixture can improve the contents of SP and VIP and the expression of c-Kit in rats with STC to some extent.

Spontaneous Contractions Augmented by Cholinergic and Adrenergic Systems in the Human Ureter

Interstitial cells of Cajal (ICC) evoke pacemaker activities in many tissues. The purpose of this study was to investigate the relationship between interstitial cell and pacemaker activity in the human ureter through the recording of spontaneous contractions. Spontaneous contractions of eight circular and longitudinal smooth muscle strips of the human ureter to acetylcholine (ACh) and/or norepinephrine (NE) were observed. Human ureteral strips were divided into proximal and distal groups, and each group was subdivided into circular and longitudinal groups. The proximal group showed spontaneous activities of 3~4 times within 5 minutes in the longitudinal group. ACh (10(-4) M) augmented the frequency of the spontaneous contractions. The cumulative application of NE also augmented the frequency in a dose-dependent manner. The effects of NE application were inhibited by concomitant application of 10(-5) M glibenclamide. Receptor tyrosine kinase (c-kit) staining revealed abundant ICCs only in proximal tissues. Therefore, spontaneous contractions of the human ureter might be modulated by ICC in the proximal region, and the actions might be related with the activation of cholinergic and/or adrenergic system mediated by a glibenclamide-sensitive pathway.

Smooth Muscles Contraction in Gastrointestinal Tract and New Concept of Enteric Neurotransmission: Fibroblast-like Cells / 대한내과학회지

This review provides information regarding an enteric neurotransmission from enteric nerve terminals to smooth muscles. In the gastrointestinal tract, phasic contractions are caused by electrical activity termed slow waves. Slow waves are generated and actively propagated by interstitial cells of Cajal (ICC). The initiation of pacemaker activity in the ICC is caused by release of Ca2+ from inositol 1, 4, 5-trisphosphate (IP3) receptor-operated stores, and the development of unitary currents. Summation of unitary currents causes depolarization and activation of a dihydropyridine-resistant Ca2+ conductance that entrains pacemaker activity in a network of ICC, resulting in the active propagation of slow waves. Slow wave frequency is regulated by a variety of physiological agonists and conditions, and shifts in pacemaker dominance can occur in response to both neural and non-neural inputs. Fibroblast-like cells (FLCs) are also closely associated with nerve varicosities and are labelled robustly with antibodies for platelet-derived growth factor receptor alpha (PDGFRalpha), and expression of this receptor may be a powerful new means of isolating and evaluating the function of FLCs and the possible contribution of these cells in disease. PDGFRalpha+ cells share similar anatomical distributions, and FLCs in colonic smooth muscle functionally express small conductance Ca(2+)-activated K+ channel (SK3). These findings are important to understand purinergic post-junctional responses.

Interstitial cell of cajal regulates motility of gallbladder smooth muscle in guinea pigs / 第二军医大学学报

Objective: To prove that the interstitial cells of cajal (ICCs) are the pacemaker of gallbladder smooth muscle in guinea pigs. Methods: The contraction of gallbladder was observed by isometric transducer and spontaneous electrophysiology was recorded in vivo and in vitro. ICCs were damaged with methylene and illumination. The ICCs were isolated by collagenase digestion and the morphology of single ICC was analyzed. C-kit expression was detected by laser confocal microscopy to identify the isolated ICCs. Spontaneous currents of ICCs were recorded with EPC-10 Patch Clamp. Results: Slow wave and action potential were recorded in gallbladder in vivo, with the frequency of slow wave being (58±3.2) bpm (n=16). Methylene blue and illumination treatment led to decrease or disappearance of slow wave and action potentials. Some cells isolated from gallbladder smooth muscle ([5±1.2]%, n=12) showed the morphological characteristics of ICCs under light microscope, with (21±4)% of the cells were positive for c-kit. When the membrane potential was at -60 mV, the frequency of spontaneous inward currents was (58.4±3.5) bpm (n=21) and the amplitude was -(72±3.5) pA. Conclusion: ICC-like cells are present in the gallbladder smooth muscle of the guinea pigs, and participate in the pacemaking of spontaneous current and action potential of gallbladder smooth muscle.

A Case of Gastrointestinal Stromal Tumor in a Child / 대한소아소화기영양학회지

Gastrointestinal stromal tumors (GISTs) are the most common primary mesenchymal tumors of the digestive tract. They have been commonly observed in adults but have been rarely described in children. They arise typically from the intestinal wall and rarely in the mesentery, omentum, or retroperitoneum. GISTs originate from the interstitial cell of Cajal and are characterized by overexpression of the receptor tyrosine kinase c-kit. Up to 94% of these tumors express the CD117 on immunohistochemical stain. Surgery is the main modality of treatment for primary resectable GIST. Completely resectable GIST with low risk has excellent prognosis after primary surgical intervention, with over 90% of the 5-year survival. We report a case of 10-year-old girl presenting with an upper gastrointestinal bleeding caused by gastrointestinal stromal tumor.

Effect of Xiaopi prescription (消痞方) on mRNA expression of c-kit in the rat with diabetic gastroparesis / 中国中西医结合急救杂志

Objective To investigate the possible role of interstitial cell of Cajal (ICE)in the pathogenesis of diabetic gastroparesis and the protective effect of"Xiaopi prescription (消痞方)".Methods Fifty healthy male Spregue-Dawley (SD) rats were randomly divided into 5 groups (each n=10):normal, model,and 3 Xiaopi prescription groups:low,middle and high dosages.Diabetes was induced by intravenous injection of alloxan,and equal amount of normal saline was intravenously injected in the normal group.Gastric lavage method was used to administer the traditional Chinese medicine decoction of Xiaopi prescription in corresponding amount (5,10 and 20 g?kg~(-1)?d~(-1)) in respective low,middle and high dosage groups.In the normal control group and diabetic model group,only equal amount of normal saline was administered into the stomach.Gastric emptying rate was measured by method of nutritious semisolid paste;c-kit positive cells of ICC were quantitatively measured with immunohistochemistry assay and computer image analysis system;c-kit mRNA positive cells were quantitatively measured with in situ hybridization and computer image analysis system.Results①Gastric emptying rate:The rate was significantly lower in the model group than that in the normal control group (P0.05),but higher than those in the model group and the low dosage group (all P0.05).②c-kit immmunohistochemistry:c-kit positive cell presented yellow in color,and its membrane was stained yellow,this kind of cells primarily were distributed around the neural plexus in the inter-space between the circular and longitudinal muscular fibers, and around the ganglionic cells forming"sheath-like"structure.The results of numbers of c-kit positive cells in the various groups:the number of the cells in the model group was significantly lower than that in the normal group (P0.05),but the numbers in the former two dosage groups were obviously higher than those in the model group (all P0.05),being significantly lower than that in the normal group,middle and high dosage groups (all P0.05),but obviously higher than those in the model group (all P0.05),being significantly lower than that in the normal,middle and high dosage groups (all P

Establishment of an animal model of slow tramit constipation and the investigation of its mechanism / 医学研究生学报

Objective:To establish an animal model of slow transit constipation and the pathobiological changes in interstitial cell of Cajal in colon. Methods:The mouse model was established by subcutaneous administration of morphine. Fecal weight was recorded daily. Transit functions of intestinal movement were examined by activated charcoal suspension pushing test and the changes of interstitial cell of Cajal were observed by immunohistochemical methods. Results:Compared with the controlled mice, there was a significant decrease in fecal weight daily(P

Changes in nitriergic nerves and interstitial cell of Cajal in intestinal myenteric plexus of scalded rat during early post-burn stage / 解放军医学杂志

Objective To study the changes in nitriergic nerves and interstitial cell of Cajal (ICC) in intestinal myenteric plexus of scalded rats during early post-burn stage. Methods 20 rats were randomly divided into scald group (n=10) and control group (n=10). A rat model of 30% TBSA with II degree scald was reproduced in the scald group. The rate of enteric transit was measured, and the histological changes in nitriergic nerves in intestinal myenteric plexus of scalded rat were observed as well. The densities of neurons and ganglions with positive nitric oxide synthetase (NOS) as well as ICC in duodenal myenteric plexus were assessed for both groups. Results In the rats in scalded group, the rate of enteric transit was prolonged, and the number of nitriergic nerves and ICC in myenteric plexus of rat duodenum were significantly decreased (P

The Gastric Motor Function in Patients with Advanced Gastric Cancer and Circular Muscle / 대한소화관운동학회지

BACKGROUND/AIMS: Gastric motor function in patients with advanced gastric cancer (AGC) may dependent upon the extent, depth of invasion, and/or location of cancer. The network of interstitial cell of Cajal (ICC) acts as a pacemaker cell to produce the slow wave, and tyrosine kinase receptor, c-kit plays an important role in development and function of the ICC. We investigated the gastric motor function in patients with advanced gastric cancer, and examined the density of c-kit+ cells in circular muscle layer of the stomach to investigate a possible correlation between gastric motor function and the density of c-kit. METHODS: The subjects include 25 patients operated for non-obstructive AGC. Preoperative electrogastrography (EGG) and gastric emptying (GE) scan were performed in all patients. The frozen samples of circular muscle without cancer infiltration in midantrum and midbody, greater curvature were prepared from resected tissue and immunohistochemistry for c-kit was performed. The density of c-kit was quantitatively analyzed. RESULTS: Several GE parameters including T(1/2) were deranged in patients with AGC, especially antral lesion. There was no significant difference in GE parameters or frequency of slow wave between antrum and body in AGC. The density of c-kit in antrum was greater trend than that in body. No correlation was found among the density of c-kit, T(1/2) and the slow wave frequency. CONCLUSIONS: We observed a delayed gastric emptying in patients with advanced gastric cancer, especially antral lesion without any abnormalities in myoelectrical activity. No correlation was found among T(1/2), slow wave frequency and c-kit density in patients with advanced gastric cancer.