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Intestinal Smooth Muscle (intestinal + smooth_muscle)
Selected AbstractsIn vitro effects of lidocaine on the contractility of equine jejunal smooth muscle challenged by ischaemia-reperfusion injuryEQUINE VETERINARY JOURNAL, Issue 1 2010M. GUSCHLBAUER Summary Reasons for performing study: Post operative ileus (POI) in horses is a severe complication after colic surgery. A commonly used prokinetic drug is lidocaine, which has been shown to have stimulatory effects on intestinal motility. The cellular mechanisms through which lidocaine affects smooth muscle activity are not yet known. Objectives: To examine the effects of lidocaine on smooth muscle in vitro and identify mechanisms by which it may affect the contractility of intestinal smooth muscle. Hypothesis: Ischaemia and reperfusion associated with intestinal strangulation can cause smooth muscle injury. Consequently, muscle cell functionality and contractile performance is decreased. Lidocaine can improve basic cell functions and thereby muscle cell contractility especially in ischaemia-reperfusion-challenged smooth muscle. Methods: To examine the effects of lidocaine on smooth muscle function directly, isometric force performance was measured in vitro in noninjured and in vivo ischaemia-reperfusion injured smooth muscle tissues. Dose-dependent response of lidocaine was measured in both samples. To assess membrane permeability as a marker of basic cell function, release of creatine kinase (CK) was measured by in vitro incubations. Results: Lidocaine-stimulated contractility of ischaemia-reperfusion injured smooth muscle was more pronounced than that of noninjured smooth muscle. A 3-phasic dose-dependency was observed with an initial recovery of contractility especially in ischaemia-reperfusion injured smooth muscle followed by a plateau phase where contractility was maintained over a broad concentration range. CK release was decreased by lidocaine. Conclusion: Lidocaine may improve smooth muscle contractility and basic cell function by cellular repair mechanisms which are still unknown. Improving contractility of smooth muscle after ischaemia-reperfusion injury is essential in recovery of propulsive intestinal motility. Potential relevance: Characterisation of the cellular mechanisms of effects of lidocaine, especially on ischaemia-reperfusion injured smooth muscle, may lead to improved treatment strategies for horses with POI. [source] Protease-Activated Receptors: A Means of Converting Extracellular Proteolysis into Intracellular SignalsIUBMB LIFE, Issue 6 2002E. J. Mackie Abstract Protease-activated receptors (PARs) mediate cellular responses to a variety of extracellular proteases. The four known PARs constitute a subgroup of the family of seven-transmembrane domain G protein-coupled receptors and activate intracellular signalling pathways typical for this family of receptors. Activation of PARs involves proteolytic cleavage of the extracellular domain, resulting in formation of a new N terminus, which acts as a tethered ligand. PAR-1, -3, and -4 are relatively selective for activation by thrombin whereas PAR-2 is activated by a variety of proteases, including trypsin and tryptase. Recent studies in mice genetically incapable of expressing specific PARs have defined roles for PAR-1 in vascular development, and for PAR-3 and -4 in platelet activation, which plays a fundamental role in blood coagulation. PAR-1 has also been implicated in a variety of other biological processes including inflammation, and brain and muscle development. Responses mediated by PAR-2 include contraction of intestinal smooth muscle, epithelium-dependent smooth muscle relaxation in the airways and vasculature, and potentiation of inflammatory responses. The area of PAR research is rapidly expanding our understanding of how cells communicate and control biological functions, in turn increasing our knowledge of disease processes and providing potential targets for therapeutic intervention. [source] Characterisation 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] Increased colonic transit in rats produced by a combination of a cholinesterase inhibitor with a 5-HT4 receptor agonistNEUROGASTROENTEROLOGY & MOTILITY, Issue 11 2009K. Campbell-dittmeyer Abstract, Increased cholinergic stimulation and accelerated gastrointestinal (GI) transit may be produced by direct stimulation of the acetylcholine (ACh) receptor with an appropriate agonist by increased release of ACh from cholinergic nerve terminals or by a decreased removal or breakdown of ACh within cholinergic synapses. The acetylcholinesterase inhibitor, neostigmine, and the 5-HT4 receptor partial agonist tegaserod, are two agents with known prokinetic activity which work by different mechanisms that result in increased levels of ACh at cholinergic synapses innervating intestinal smooth muscle. Here, we aimed to investigate the potential synergistic effect on colonic transit that may occur with concomitant use of these two agents. Colonic transit was indirectly assessed in rats via measurements of fecal pellet output every 30 min for 2.5 h following administration of neostigmine (0.003,0.1 mg kg,1, i.p.), tegaserod (0.01,1.0 mg kg,1, i.p.), or a combination of both compounds. When administered alone, neostigmine or tegaserod caused a dose-dependent increase in fecal pellet output. In combination, low doses of the two agents which did not produce statistically significant effects alone, compared to the vehicle, caused a significant increase in fecal pellet output. Combinations of higher doses of neostigmine and tegaserod did not display synergy. In summary, when combined at low doses, neostigmine and tegaserod produce synergistic effects manifested by a statistically significant increase in the expulsion of fecal pellets. A combination of an anticholinesterase agent with a 5-HT4 receptor agonist may prove to be a useful therapeutic approach to treat conditions associated with slow GI transit. [source] Smooth muscle phenotypic plasticity in mechanical obstruction of the small intestineNEUROGASTROENTEROLOGY & MOTILITY, Issue 7 2008J. A. Macdonald Abstract, Chronic, partial obstruction of the small intestine can dramatically alter peristaltic contractile properties. Morphological studies have revealed hypertrophy of the circular smooth muscle cells in the constricted part of the intestine. In this issue of Neurogastroenterology and Motility, Chen et al. show that hyperplasia and hypertrophy of intestinal smooth muscle cells occur at distinct times in response to partial obstruction of the ileum. Furthermore, the first evidence is provided to link intestinal smooth muscle remodelling during mechanical obstruction with changes in serum response factor and two of its co-regulating factors, myocardin and Elk-1. [source] Diabetes and the enteric nervous systemNEUROGASTROENTEROLOGY & MOTILITY, Issue 12 2007B. Chandrasekharan Abstract, Diabetes is associated with several changes in gastrointestinal (GI) motility and associated symptoms such as nausea, bloating, abdominal pain, diarrhoea and constipation. The pathogenesis of altered GI functions in diabetes is multifactorial and the role of the enteric nervous system (ENS) in this respect has gained significant importance. In this review, we summarize the research carried out on diabetes-related changes in the ENS. Changes in the inhibitory and excitatory enteric neurons are described highlighting the role of loss of inhibitory neurons in early diabetic enteric neuropathy. The functional consequences of these neuronal changes result in altered gastric emptying, diarrhoea or constipation. Diabetes can also affect GI motility through changes in intestinal smooth muscle or alterations in extrinsic neuronal control. Hyperglycaemia and oxidative stress play an important role in the pathophysiology of these ENS changes. Antioxidants to prevent or treat diabetic GI motility problems have therapeutic potential. Recent research on the nerve,immune interactions demonstrates inflammation-associated neurodegeneration which can lead to motility related problems in diabetes. [source] Actions of R- and S-verapamil and nifedipine on rat vascular and intestinal smooth muscleAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 3 2004L. Cleary Summary 1 We have investigated the actions of the calcium entry blockers nifedipine, R-verapamil and S-verapamil in rat aorta, colon and vas deferens. 2 In aorta and colon, these agents produced concentration-dependent relaxations of KCl (80 mm)-induced contractions. In both tissues, the order of potency was nifedipine > S-verapamil > R-verapamil. However, nifedipine showed selectivity for aorta (potency ratio, colon/aorta: 4.36), S-verapamil showed no selectivity (0.62), but R-verapamil showed selectivity for colon (0.19). 3 In prostatic portions of rat vas deferens, nifedipine (10 ,m) abolished the contraction to a single electrical stimulus, but R- and S-verapamil were without effect. In epididymal portions of rat vas deferens, R- and S-verapamil inhibited ,1 -adrenoceptor-mediated contractions to a single electrical stimulus at concentrations of 10 ,m and above. 4 In conclusion, R-verapamil may prove useful as an intestinal selective calcium entry blocker in the treatment of intestinal disease with a hypermotility component, e.g. irritable bowel syndrome. [source] | ||||||||||