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Human Sigmoid Colon (human + sigmoid_colon)
Selected AbstractsEffect of otilonium bromide on contractile patterns in the human sigmoid colonNEUROGASTROENTEROLOGY & MOTILITY, Issue 6 2010D. Gallego Abstract Background, The mechanism of action of the spasmolytic compound otilonium bromide (OB) on human colonic motility is not understood. The aim of our study was to characterize the pharmacological effects of OB on contractile patterns in the human sigmoid colon. Methods, Circular sigmoid strips were studied in organ baths. Isolated smooth muscle cells from human sigmoid colon were examined using the calcium imaging technique. Key Results, Otilonium bromide inhibited by 85% spontaneous non-neural rhythmic phasic contractions (RPCs), (IC50 = 49.9 nmol L,1) and stretch-induced tone (IC50 = 10.7 nmol L,1) with maximum effects at micromolar range. OB also inhibited by 50% both on- (IC50 = 38.0 nmol L,1) and off- contractions induced by electrical stimulation of excitatory motor neurons. In contrast, the inhibitory latency period prior to off -contractions was unaffected by OB. OB inhibited acetylcholine-, substance P-, and neurokinin A-induced contractions. The L-type Ca2+ channel agonist BayK8644 reversed the effects of OB on RPCs, on- and off -contractions. Hexamethonium, atropine, the NK2 antagonist, or depletion of intracellular Ca2+ stores by thapsigargin did not prevent the inhibitory effect of OB on RPCs and electrical contractions. KCl-induced calcium transients in isolated smooth muscle cells were also inhibited by OB (IC50 = 0.2 ,mol L,1). Conclusions & Inferences, Otilonium bromide strongly inhibited the main patterns of human sigmoid motility in vitro by blocking calcium influx through L-type calcium channels on smooth muscle cells. This pharmacological profile may mediate the clinically observed effects of the drug in patients with irritable bowel syndrome. [source] Distribution of serotonin receptors and interacting proteins in the human sigmoid colonNEUROGASTROENTEROLOGY & MOTILITY, Issue 5 2009N. Chetty Abstract, This study aimed to examine the distribution of 5-HT receptors in the human colon. 5-HT induces desensitization of the circular muscle and as this is facilitated by G-protein coupled receptor kinases (GRKs) and other proteins, we also examined their distribution. Human sigmoid colon samples were dissected into three separate layers (mucosa, taeniae coli and intertaenial strips) and RNA was amplified by RT-PCR. The 5-HT2B receptor and all 5-HT7 receptor splice variants were expressed in all tissues. 5-HT4 a,b,c and n splice variants were also expressed in all tissues and 5-HT4d, 5-HT4g and 5-HT4i were only detected in some samples. The 5-HT2A receptor was seen predominantly in the intertaenial strips of the colon. Only one transcript of the serotonin transporter (SERT) was detected in the muscle layers. Variation was seen in GRK expression with GRK2 and 3 predominantly expressed in the mucosa, while GRK5 and 6 were found more commonly in the taeniae coli. PDZ (named after postsynaptic density protein, Drosophila disc large tumour suppressor and tight junction protein ZO-1) domain containing proteins, which may be involved in 5-HT receptor trafficking, were also detected throughout the sigmoid colon. The 5-HT3A subunit was expressed in all tissues, whereas the 5-HT3E subunit was mainly found in the mucosa layer while the 5-HT3B subunit was more common in the muscle layers. Receptor interacting chaperone (RIC-3), which is involved in transporting 5-HT3 receptor subunits, is expressed less in mucosa compared to muscle layers. In conclusion, these results show that there is variation in distribution of 5-HT receptors and interacting proteins within the sigmoid colon that may contribute to colonic function. [source] Effects of excitatory and inhibitory neurotransmission on motor patterns of human sigmoid colon in vitroBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2008M Aulí Background and purpose: To characterize the in vitro motor patterns and the neurotransmitters released by enteric motor neurons (EMNs) in the human sigmoid colon. Experimental approach: Sigmoid circular strips were studied in organ baths. EMNs were stimulated by electrical field stimulation (EFS) and through nicotinic ACh receptors. Key results: Strips developed weak spontaneous rhythmic contractions (3.67±0.49 g, 2.54±0.15 min) unaffected by the neurotoxin tetrodotoxin (TTX; 1 ,M). EFS induced strong contractions during (on, 56%) or after electrical stimulus (off, 44%), both abolished by TTX. Nicotine (1,100 ,M) inhibited spontaneous contractions. Latency of off-contractions and nicotine responses were reduced by NG -nitro- L -arginine (1 mM) and blocked after further addition of apamin (1 ,M) or the P2Y1 receptor antagonist MRS 2179 (10 ,M) and were unaffected by the P2X antagonist NF279 (10 ,M) or ,-chymotrypsin (10 U mL,1). Amplitude of on- and off-contractions was reduced by atropine (1 ,M) and the selective NK2 receptor antagonist Bz-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (1 ,M). MRS 2179 reduced the amplitude of EFS on- and off-contractions without altering direct muscular contractions induced by ACh (1 nM,1 mM) or substance P (1 nM,10 ,M). Conclusions and implications: Latency of EFS-induced off-contractions and inhibition of spontaneous motility by nicotine are caused by stimulation of inhibitory EMNs coreleasing NO and a purine acting at muscular P2Y1 receptors through apamin-sensitive K+ channels. EFS-induced on- and off-contractions are caused by stimulation of excitatory EMNs coreleasing ACh and tachykinins acting on muscular muscarinic and NK2 receptors. Prejunctional P2Y1 receptors might modulate the activity of excitatory EMNs. P2Y1 and NK2 receptors might be therapeutic targets for colonic motor disorders. British Journal of Pharmacology (2008) 155, 1043,1055; doi:10.1038/bjp.2008.332; published online 1 September 2008 [source] Numerical distribution of lymphoid nodules in the human sigmoid colon, rectosigmoidal junction, rectum, and anal canalCLINICAL ANATOMY, Issue 2 2006Ivan L. Cameron Abstract There is little information on the numerical distribution of lymphoid nodules (LN) in distal segments of the human large bowel. A novel approach was therefore developed to assess the number of LN in the sigmoid colon, the rectosigmoid segment, the rectum, and the anal canal in humans. The distal large bowel from five cadavers was selected for quantitative study. The number of LN was scored macroscopically from the proximal sigmoid colon to the distal anal canal. A numerical distribution, previously unreported, consisting of two circular bands of LN was observed in each of the five cadavers. One band was located 3 cm proximal from the pectinate line and the other was located at the rectosigmoid segment. Significantly more LN occurred 3,5 cm proximal to the pectinate line compared to areas distal or proximal to this band of LN. This band of LN has not been reported previously in humans. Clin. Anat. 19:164,170, 2006. © 2006 Wiley-Liss, Inc. [source] |