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Mouse Colon (mouse + colon)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	50%

Selected Abstracts

Differential effects of CB1 neutral antagonists and inverse agonists on gastrointestinal motility in mice

NEUROGASTROENTEROLOGY & MOTILITY, Issue 7 2010
M. 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]

Bimodal Oscillation Frequencies of Blood Flow in the Inflammatory Colon Microcirculation

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 1 2009
Akira Tsuda
Abstract Rhythmic changes in blood flow direction have been described in the mucosal plexus of mice with acute colitis. In this report, we studied mice with acute colitis induced either by dextran sodium sulfate or by trinitrobenzenesulfonic acid. Both forms of colitis were associated with blood flow oscillations as documented by fluorescence intravital videomicroscopy. The complex oscillation patterns suggested more than one mechanism for these changes in blood flow. By tracking fluorescent nanoparticles in the inflamed mucosal plexus, we identified two forms of blood flow oscillations within the inflammatory mouse colon. Stable oscillations were associated with a base frequency of approximately 2 cycles/sec. Velocity measurements in the upstream and downstream vessel segments indicated that stable oscillations were the result of regional flow occlusion within the mucosal plexus. In contrast, metastable oscillations demonstrated a lower frequency (0.2,0.4 cycles/sec) and appeared to be the result of flow dynamics in vessels linked by the bridging mucosal vessels. These blood flow oscillations were not directly associated with cardiopulmonary movement. We conclude that both the stable and metasable oscillating patterns reflect flow adaptations to inflammatory changes in the mucosal plexus. Anat Rec, 2009. © 2008 Wiley-Liss, Inc. [source]

Bridging Mucosal Vessels Associated with Rhythmically Oscillating Blood Flow in Murine Colitis

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 1 2008
Aslihan Turhan
Abstract Oscillatory blood flow in the microcirculation is generally considered to be the result of cardiopulmonary influences or active vasomotion. In this report, we describe rhythmically oscillating blood flow in the bridging vessels of the mouse colon that appeared to be independent of known biological control mechanisms. Corrosion casting and scanning electron microscopy of the mouse colon demonstrated highly branched bridging vessels that connected the submucosal vessels with the mucosal plexus. Because of similar morphometric characteristics (19 ± 11 ,m vs. 28 ± 16 ,m), bridging arterioles and venules were distinguished by tracking fluorescent nanoparticles through the microcirculation using intravital fluorescence videomicroscopy. In control mice, the blood flow through the bridging vessels was typically continuous and unidirectional. In contrast, two models of chemically induced inflammation (trinitrobenzenesulfonic acid and dextran sodium sulfate) were associated with a twofold reduction in flow velocity and the prominence of rhythmically oscillating blood flow. The blood oscillation was characterized by tracking the bidirectional displacement of fluorescent nanoparticles. Space,time plots and particle tracking of the oscillating segments demonstrated an oscillation frequency between 0.2 and 5.1 cycles per second. Discrete Fourier transforms demonstrated a power spectrum composed of several base frequencies. These observations suggest that inflammation-inducible changes in blood flow patterns in the murine colon resulted in both reduced blood flow velocity and rhythmic oscillations within the bridging vessels of the mouse colon. Anat Rec, 291:74,82, 2007. © 2007 Wiley-Liss, Inc. [source]

Effects of female steroid hormones on A-type K+ currents in murine colon

THE JOURNAL OF PHYSIOLOGY, Issue 2 2006
Elizabeth A. H. Beckett
Idiopathic constipation is higher in women of reproductive age than postmenopausal women or men, suggesting that female steroid hormones influence gastrointestinal motility. How female hormones affect motility is unclear. Colonic motility is regulated by ion channels in colonic myocytes. Voltage-dependent K+ channels serve to set the excitability of colonic muscles. We investigated regulation of Kv4.3 channel expression in response to acute or chronic changes in female hormones. Patch clamp experiments and quantitative PCR were used to compare outward currents and transcript expression in colonic myocytes from male, non-pregnant, pregnant and ovariectomized mice. Groups of ovariectomized mice received injections of oestrogen or progesterone to investigate the effects of hormone replacement. The capacitance of colonic myocytes from non-pregnant females was larger than in males. Net outward current density in male and ovariectomized mice was higher than in non-pregnant females and oestrogen-treated ovariectomized mice. Current densities in late pregnancy were lower than in female controls. Progesterone had no effect on outward currents. A-type currents were decreased in non-pregnant females compared with ovariectomized mice, and were further decreased by pregnancy or oestrogen replacement. Kv4.3 transcripts did not differ significantly between groups; however, expression of the potassium channel interacting protein KChIP1 was elevated in ovariectomized mice compared with female controls and oestrogen-treated ovariectomized mice. Delayed rectifier currents were not affected by oestrogen. In the mouse colon, oestrogen suppresses A-type currents, which are important for regulating excitability. These observations suggest a possible link between female hormones and altered colonic motility associated with menses, pregnancy and menopause. [source]

The regulation of veratridine-stimulated electrogenic ion transport in mouse colon by neuropeptide Y (NPY), Y1 and Y2 receptors

BRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2005
Niall P Hyland
Neuropeptide Y (NPY) is a prominent enteric neuropeptide with prolonged antisecretory effects in mammalian intestine. Veratridine depolarises neurons consequently causing epithelial anion secretion across mouse colon mucosa. Our aim was to characterise functionally, veratridine-stimulated mucosal responses and to determine the roles for NPY, Y1, and Y2 receptors in modulating these neurogenic effects. Colon mucosae (with intact submucous innervation) from wild-type mice (+/+) and knockouts lacking either NPY (NPY,/,), Y1,/, or Y2,/, were placed in Ussing chambers and voltage clamped at 0 mV. Veratridine-stimulated short-circuit current (Isc) responses in +/+, Y1 or Y2 antagonist pretreated +/+ colon, Y1,/, and NPY,/, colon were insensitive to cholinergic blockade by atropine (At; 1 ,M) and hexamethonium (Hex; 10 ,M). Tetrodotoxin (TTX, 100 nM) abolished veratridine responses, but had no effect upon carbachol (CCh) or vasoactive intestinal polypeptide (VIP)-induced secretory responses. To establish the functional roles for Y1 and Y2 receptors, +/+ tissues were pretreated with either the Y1 or Y2 receptor antagonist (BIBO3304 (300 nM) or BIIE0246 (1 ,M), respectively) and veratridine responses were compared with those from Y1,/, or Y2,/, colon. Neither BIBO3304 nor Y1,/, altered veratridine-induced secretion, but Y1 agonist responses were abolished in both preparations. In contrast, the Y2 antagonist BIIE0246 significantly amplified veratridine responses in +/+ mucosa. Unexpectedly, NPY,/, colon exhibited significantly attenuated veratridine responses (between 1 and 5 min). We demonstrate that electrogenic veratridine responses in mouse colon are noncholinergic and that NPY can act directly upon epithelia, a Y1 receptor effect. The enhanced veratridine response observed in +/+ tissue following BIIE0246, indicates that Y2 receptors are located on submucosal neurons and that their activation by NPY will inhibit enteric noncholinergic secretory neurotransmission. We also demonstrate Y1 and Y2 receptor-mediated antisecretory tone in +/+ colon and show selective loss of each in Y1 and Y2 null colon respectively. In NPY,/, tissue, only Y1 -mediated tone was present, this presumably being mediated by endogenous endocrine peptide YY. Y2 tone was absent from NPY,/, (and Y2,/,) colon and we conclude that NPY activation of neuronal Y2 receptors attenuates secretory neurotransmission thereby providing an absorptive electrolyte tone in isolated colon. British Journal of Pharmacology (2005) 146, 712,722. doi:10.1038/sj.bjp.0706368 [source]

Consequences of Citrobacter rodentium infection on enteroendocrine cells and the enteric nervous system in the mouse colon

CELLULAR MICROBIOLOGY, Issue 4 2006
Jennifer R. O'Hara
Summary We tested the hypothesis that Citrobacter rodentium infection leads to changes in the mucosal enteroendocrine signalling and the enteric nervous system and that the host's immune response contributes to these changes. Enteroendocrine cells, serotonin (5-HT) reuptake transporter (SERT), 5-HT release, and inducible nitric oxide synthase (iNOS) expression were assessed in the colon of infected wild-type or severe combined immunodeficient (SCID) mice. Immunoreactivity for iNOS and neuropeptides were examined in the submucosal and myenteric plexuses. Mice were orogastrically infected with C. rodentium and experiments were conducted during the injury phase (10 days) and the recovery phase (30 days). 5-HT and somatostatin enteroendocrine cells and SERT were significantly reduced 10 days after infection, with numbers returning to control values at 30 days. 5-HT release was increased at 10 days. Changes to the mucosal serotonin signalling system were not observed in SCID mice. iNOS immunoreactivity was increased in the submucosa and mucosa at 10 days and returned to baseline levels by 30 days. No differences were observed in neuropeptide or iNOS immunoreactivity in the enteric plexuses following infection. The host's immune response underlies changes to enteroendocrine cells, SERT expression and 5-HT release in C. rodentium infection. These changes could contribute to disturbances in gut function arising from enteric infection. [source]

ARE GAP JUNCTIONS TRULY INVOLVED IN INHIBITORY NEUROMUSCULAR INTERACTION IN MOUSE PROXIMAL COLON?

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2006
Andrei Sibaev
SUMMARY 1Gap junctions exist between circular muscle cells of the colon and between interstitial cells of Cajal (ICC) in the myenteric plexus of the gastrointestinal tract. They also probably couple intramuscular ICC with smooth muscle cells. Recent functional evidence for this was found in dye-coupling and myoelectrical experiments. 2In the present study, we tested the hypothesis of gap junctions putatively being involved in neuromuscular interaction in mouse colon by using different classes of gap junction blockers. 3Electrical field stimulation of the myenteric plexus elicited tetrodotoxin-sensitive and hexamethonium-independent fast and slow inhibitory junction potentials (fIJP and sIJP, respectively) in circular smooth muscle cells, as evaluated by intracellular recording techniques in impaled smooth muscle cells. Heptanol produced a time-dependent hyperpolarization of the membrane potential (MP) and abolished fIJP and sIJP. Octanol had no effect on the MP and abolished fIJP and sIJP. Carbenoxolone produced a time-dependent depolarization of the MP without any effect on fIJP or sIJP. The connexin 43 mimetic gap junction blocker GAP-27 had no effect on MP, fIJP or sIJP. 4Based on the presently available gap junction blockers we found no evidence that gap junctions are involved in neuromuscular transmission in mouse colon, as suggested by morphological studies. [source]