Home About us Contact
|
Home About us Contact | ||
|
|
||
Mouse Ileum (mouse + ileum)
Selected AbstractsCharacterisation of the effects of potassium channel modulating agents on mouse intestinal smooth muscleJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2002Chi-Kong Yeung The actions of agents which modulate ATP-sensitive potassium (KATP) channels in excitable cells were investigated in an in-vitro preparation of mouse ileum from which the mucosa was removed. A range of potassium channel openers of diverse structure, cromakalim (0.1,100 ,M), pinacidil (0.1,200 ,M) and its analogue P1060 (0.1,200 ,M), SDZ PCO400 ((-)-(3S,4R)-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(3-oxo-cyclopent-1-enyloxy)-2H -1-benzopyran-6-carbonitrile) (0.3,60 ,M), caused concentration-related reduction in twitch height of electrical field stimulated ileum. P1060 and SDZ PCO400 were the most potent agents; diazoxide (0.1,100 ,M) was without effect. The order of inhibitory potency, based on EC50 values (concentration of a relaxant producing 50% of the maximum inhibition of twitch) was: P1060 = SDZ PCO400 > cromakalim > pinacidil. The relaxant effect of the potassium channel openers was antagonised by the sulfonylureas glibenclamide (0.1-1.0 ,M) and glipizide (3,30 ,M) but the nature of the antagonism differed. Antagonism of P1060 and SDZ PCO400 by glibenclamide appeared to be competitive whereas the antagonism of relaxation induced by cromakalim and pinacidil was apparently not competitive. Both phentolamine (1,10 ,M) and tolbutamide (100,300 ,M) showed competitive antagonism of the actions of pinacidil while yohimbine (1,20 ,M) did not antagonise relaxation and appeared to have actions at sites other than the KATP channel in this preparation. The relative effectiveness of the antagonists on pinacidil-induced relaxation was found to be: glibenclamide >phentolamine >tolbutamide >yohimbine, which is in agreement with studies in other tissues. The results show that many structurally diverse potassium channel openers are potent relaxants of mouse ileum. These observations are consistent with the existence of ATP-dependent K+ channels in murine intestinal muscle which, however, differ somewhat in properties from those reported for vascular muscle and pancreatic ,-cells. [source] Taurocholic acid-induced secretion in normal and cystic fibrosis mouse ileumJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2001J. Hardcastle Bile acids cause secretion throughout the intestinal tract and this process contributes to maintaining the fluidity of intestinal contents. In cystic fibrosis (CF) defective intestinal secretion can lead to excessive dehydration of the luminal contents and the development of clinical symptoms. This study was designed to investigate bile acid-induced secretion in mouse ileum and to determine whether this process was defective in CF. Taurocholic acid-induced secretion was monitored as a rise in short-circuit current (SCC) in ileal sheets from normal (Swiss MF1) and transgenic CF mice. Taurocholic acid increased the SCC in both intact and stripped ileal sheets from Swiss MF1 mice. This effect was due to a stimulation of electrogenic Cl, secretion as it was inhibited by Cl, -free conditions, serosal furosemide (frusemide), mucosal diphenylamine-2-carboxylic acid (DPC) and increased serosal K+ concentration, without being affected by reduced mucosal Na+ concentration. Taurocholic acid-induced secretion was inhibited by tetrodotoxin, indicating the involvement of a neural pathway, but this did not include capsaicin-sensitive afferent neurons or muscarinic cholinoreceptors. Mucosal mast cells also contributed to the response. Responses in tissues from transgenic wild-type mice were similar to those obtained with Swiss MF1 animals, but ilea from CF mice exhibited a lower basal SCC with significantly reduced secretory responses to acetylcholine and taurocholic acid. We concluded that taurocholic acid induces ileal secretion by a mechanism that entails activation of enteric nerves and degranulation of mucosal mast cells. Impaired bile acid-induced secretion in CF may contribute to luminal dehydration. [source] Differential effects of CB1 neutral antagonists and inverse agonists on gastrointestinal motility in miceNEUROGASTROENTEROLOGY & MOTILITY, Issue 7 2010M. A. Storr Abstract Background, Cannabinoid type 1 (CB1) receptors are involved in the regulation of gastrointestinal (GI) motility and secretion. Our aim was to characterize the roles of the CB1 receptor on GI motility and secretion in vitro and in vivo by using different classes of CB1 receptor antagonists. Methods, Immunohistochemistry was used to examine the localization of CB1 receptor in the mouse ileum and colon. Organ bath experiments on mouse ileum and in vivo motility testing comprising upper GI transit, colonic expulsion, and whole gut transit were performed to characterize the effects of the inverse agonist/antagonist AM251 and the neutral antagonist AM4113. As a marker of secretory function we measured short circuit current in vitro using Ussing chambers and stool fluid content in vivo in mouse colon. We also assessed colonic epithelial permeability in vitro using FITC-labeled inulin. Key Results,In vivo, the inverse agonist AM251 increased upper GI transit and whole gut transit, but it had no effect on colonic expulsion. By contrast, the neutral antagonist AM4113 increased upper GI transit, but unexpectedly reduced both colonic expulsion and whole gut transit at high, but not lower doses. Conclusions & Inferences, Cannabinoid type 1 receptors regulate small intestinal and colonic motility, but not GI secretion under physiological conditions. Cannabinoid type 1 inverse agonists and CB1 neutral antagonists have different effects on intestinal motility. The ability of the neutral antagonist not to affect whole gut transit may be important for the future development of CB1 receptor antagonists as therapeutic agents. [source] GABAB receptor function in the ileum and urinary bladder of wildtype and GABAB1 subunit null miceAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 3 2002G. J. Sanger Summary1 GABAB1 receptor subunit knockout mice were generated and the effects of the GABAB receptor agonist, baclofen, were evaluated within the peripheral nervous system (PNS) of wildtype (+/+), heterozygote (+/,) and knockout (,/,) animals. For this purpose, neuronally-mediated responses were evoked in both the isolated ileum and urinary bladder, using selective electrical field stimulation (EFS). 2 In ileum resected from 4,8-week-old-mice, low frequencies of EFS (0.5 Hz) evoked irregular muscle contractions which were prevented by atropine 1 ,M and reduced by baclofen (33.4 ± 5.6%, 100 ,m). The latter effect was antagonized by the GABAB receptor antagonist CGP54626 0.2 ,m. Baclofen 100 ,m did not affect contractions of similar amplitude induced by carbachol, indicating that the ability of baclofen to inhibit cholinergic function in mouse ileum may be due to an action at prejunctional GABAB receptors. 3 To avoid the development of grand mal seizure by GABAB1 (,/,) mice, a behaviour observed when the mice were greater than 3 weeks old, it was necessary to study the effects of this knockout in 1,3-week-old-animals. However, at this age, EFS at 0.5 Hz did not evoke robust muscle contractions. Consequently we used EFS at 5 Hz, which did evoke cholinergically mediated contractions, found to be of similar amplitude in (+/+) and (+/,) mice, of both 1,3 weeks and 4,8 weeks of age. At this frequency of EFS, baclofen reduced the amplitude of the evoked contractions [n=6 (+/+) and n=5 (+/,), IC50 19.2 ± 4.8 ,m) and this effect was greatly reduced in the presence of CGP54626 0.2 ,m. 4 In urinary bladder from 1,3-week-old-mice, using higher frequencies of EFS to evoke clear, nerve-mediated contractions (10 Hz), baclofen 10,300 ,m concentration-dependently inhibited contractions in (+/+) mice (IC50 9.6 ± 3.8 ,m). This effect was inhibited by CGP54626 (0.2 ,m, 46.2 ± 13.6% inhibition, 300 ,m baclofen n=7) a concentration which, by itself, had no effect on the EFS-evoked contractions. 5 The effects of baclofen in both ileum and urinary bladder were absent in the GABAB1 receptor subunit (,/,) mice; however, responses to EFS were unaffected in (,/,) when compared to the (+/+) mice. 6 Our data suggest that, as in the central nervous system (CNS), the GABAB1 receptor subunit is an essential requirement for GABAB receptor function in the enteric and PNS. As such, these data do not provide a structural explanation for the existence of putative subtypes of GABAB receptor, suggested by studies such as those in which different rank-orders of GABAB agonist affinity have been reported in different tissues. [source] | ||||||||||