Neural regulation of in vitro giant contractions in the rat colon

2001 ◽  
Vol 281 (1) ◽  
pp. G275-G282 ◽  
Author(s):  
Asensio Gonzalez ◽  
Sushil K. Sarna
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Sch 23390 ◽  
Circular Muscle ◽  
Electrical Field Stimulation ◽  
Muscle Cells ◽  
Enteric Neurons ◽  
Rat Colon ◽  
Spontaneous Contractions

The rat middle colon spontaneously generates regularly occurring giant contractions (GCs) in vitro. We investigated the neurohumoral and intracellular regulation of these contractions in a standard muscle bath. cGMP content was measured in strips and single smooth muscle cells. The circular muscle strips generated spontaneous GCs. Their amplitude and frequency were significantly increased by tetrodotoxin (TTX), ω-conotoxin, N ω-nitro-l-arginine (l-NNA), and the dopamine D1 receptor antagonist Sch-23390. The GCs were unaffected by hexamethonium, atropine, and antagonists of serotonergic (5-HT1–4), histaminergic (H1–2), and tachykininergic (NK1–2) receptors but enhanced by NK3receptor antagonism. The guanylate cyclase inhibitor 1H-[1,2,4]oxidiazolo[4,3-a]quinoxalin-1-one (ODQ) also enhanced GCs to the same extent as TTX and l-NNA, and each of the three agents prevented the effects of the others. GCs were abolished by electrical field stimulation, S-nitroso- N-acetyl-penicillamine, and 8-bromo-cGMP. BAY-K-8644 and apamin enhanced the GCs, but they were abolished by D-600. Basal cGMP content in strips was decreased by TTX,l-NNA, or ODQ, but these treatments had no effect on cGMP content of enzymatically dissociated single smooth muscle cells. We conclude that spontaneous contractions in the rat colonic muscle strips are not generated by cholinergic, serotonergic, or histaminergic input. Constitutive release of nitric oxide from enteric neurons sustains cGMP synthesis in the colonic smooth muscle to suppress spontaneous in vitro GCs.

scholarly journals Dextran Sodium Sulphate (DSS)-Induced Colitis Alters the Expression of Neurotrophins in Smooth Muscle Cells of Rat Colon

2017 ◽  
pp. 1009-1020 ◽  
Author(s):  
M. AL-QUDAH ◽  
D. A. SHAMMALA ◽  
A. AL-DWAIRI ◽  
O. AL-SHBOUL ◽  
A. G. MUSTAFA
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Longitudinal Muscle ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Muscle Layer ◽  
Sodium Sulphate ◽  
Enteric Neurons ◽  
Rat Colon ◽  
Dextran Sodium Sulphate

Neurotrophins are present in the gastrointestinal tract where they participate in the survival and growth of enteric neurons, augmentation of enteric circuits, elevation of colonic myoelectrical activity and also in different aspects of colitis. Previous studies largely focused on the role of neural and mucosal neurotrophins in gut inflammation. The expression of neurotrophins in colonic smooth muscle cells (SMCs) and the interactions of this potential source with colitis has not been studied in the gut. The expression of NGF, BDNF, NT-3 and NT-4 in SMCs from longitudinal and circular muscle layers of rat colon from normal and dextran sodium sulphate (DSS)-induced colitis rats was measured by ELISA. NGF, BDNF, NT-3 and NT-4 are differentially expressed in both longitudinal and circular SMCs, where the expressions of BDNF and NT-4 proteins were greater in SMCs from the longitudinal muscle layer than from the circular muscle layer, while NGF protein expression was greater in circular SMCs and NT-3 expression was equal in cells from both muscle layers. Induction of colitis with DSS significantly alters neurotrophins expression pattern in colonic SMCs. NGF levels upregulated in circular SMCs. BDNF level was increased in DSS-induced colitis in longitudinal SMCs. NGF, NT-3 and NT-4 levels were downregulated in longitudinal SMCs of DSS-induced colitis rats' colon. Disturbances of neurotrophins expression in SMCs resulted from colitis might account for the structural and functional changes in inflammatory bowel disease (IBD) such as loss of innervation and characteristic hypercontractility of longitudinal muscle in IBD.

Are interstitial cells of Cajal plurifunction cells in the gut?

2008 ◽  
Vol 294 (2) ◽  
pp. G372-G390 ◽  
Author(s):  
Sushil K. Sarna
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Interstitial Cells Of Cajal ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Interstitial Cells ◽  
Slow Waves ◽  
Enteric Neurons ◽  
Motility Disorders ◽  
Cells Of Cajal

The proposed functions of the interstitial cells of Cajal (ICC) are to 1) pace the slow waves and regulate their propagation, 2) mediate enteric neuronal signals to smooth muscle cells, and 3) act as mechanosensors. In addition, impairments of ICC have been implicated in diverse motility disorders. This review critically examines the available evidence for these roles and offers alternate explanations. This review suggests the following: 1) The ICC may not pace the slow waves or help in their propagation. Instead, they may help in maintaining the gradient of resting membrane potential (RMP) through the thickness of the circular muscle layer, which stabilizes the slow waves and enhances their propagation. The impairment of ICC destabilizes the slow waves, resulting in attenuation of their amplitude and impaired propagation. 2) The one-way communication between the enteric neuronal varicosities and the smooth muscle cells occurs by volume transmission, rather than by wired transmission via the ICC. 3) There are fundamental limitations for the ICC to act as mechanosensors. 4) The ICC impair in numerous motility disorders. However, a cause-and-effect relationship between ICC impairment and motility dysfunction is not established. The ICC impair readily and transform to other cell types in response to alterations in their microenvironment, which have limited effects on motility function. Concurrent investigations of the alterations in slow-wave characteristics, excitation-contraction and excitation-inhibition couplings in smooth muscle cells, neurotransmitter synthesis and release in enteric neurons, and the impairment of the ICC are required to understand the etiologies of clinical motility disorders.

scholarly journals Role of PGE2 in colonic motility: PGE2 attenuates spontaneous contractions of circular smooth muscle via EP4 receptors in the rat colon

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Shin-Ichiro Karaki ◽  
Ryo Tanaka
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Critical Role ◽  
Colonic Motility ◽  
Protein A ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Rat Colon ◽  
Colonic Tissue ◽  
Circular Smooth Muscle

AbstractColonic motor activity is important for the formation and propulsion of feces. The production of prostaglandins (PGs) in colonic tissue is considered to play a critical role in the generation and regulation of colonic motility. In this study, we investigated the inhibitory effects of PGE2 and selective agonists of four EP receptors on the spontaneous phasic contractions, called ‘giant contractions’ (GCs), of mucosa-free circular smooth muscle strips from the rat middle colon. Neural blockade with tetrodotoxin (TTX) increased the frequency and amplitude of the GCs by about twofold. However, inhibiting PG production with piroxicam reduced the GC frequency in the presence of TTX, but did not affect the GC amplitude. In the presence of both TTX and piroxicam, exogenous PGE2 and each EP receptor agonist were cumulatively added to the tissue bath. In this setting, PGE2, the EP2 agonist ONO-AE1-259, and the EP4 agonist ONO-AE1-329, but not the EP1 agonist ONO-AE-DI-004 or the EP3 agonist ONO-AE-248, concentration-dependently reduced the GC frequency and amplitude. The PGE2-induced inhibition of GC frequency and amplitude was inhibited by the EP4 antagonist ONO-AE3-208, but not by the EP1/2 antagonist AH6809. Immunohistochemistry revealed the EP2 and EP4 receptors were localized in perinuclear sites in circular smooth muscle cells. EP2 immunoreactivity was also located in GFAP-immunoreactive enteroglia, whereas EP4 immunoreactivity was also located in HU (embryonic lethal, abnormal vision [ELAV] protein; a marker of all myenteric neurons)-immunoreactive myenteric nerve cell bodies. These results suggest that the PGs produced in the colonic tissue inhibit the GC frequency and amplitude of circular muscle in the rat middle colon, and is mediated by EP4 receptors expressed in the smooth muscle cells.

Mitogenic factors promoting intestinal smooth muscle cell proliferation

2010 ◽  
Vol 299 (4) ◽  
pp. C805-C817 ◽  
Author(s):  
Roger D. P. Stanzel ◽  
Sandra Lourenssen ◽  
Dileep G. Nair ◽  
Michael G. Blennerhassett
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Primary Cultures ◽  
Muscle Cells ◽  
Rat Colon ◽  
Intestinal Smooth Muscle ◽  
Trinitrobenzene Sulfonic Acid

Intestinal smooth muscle cells are normally quiescent, but in the widely studied model of trinitrobenzene sulfonic acid (TNBS)-induced colitis in the rat, the onset of inflammation causes proliferation that leads to increased cell number and an altered phenotype. The factors that drive this are unclear and were studied in primary cultures of circular smooth muscle cells (CSMC) from the rat colon. While platelet-derived growth factor (PDGF)-AA, fibroblast growth factor (FGF), and epidermal growth factor (EGF) were ineffective, PDGF-BB and insulin-like growth factor-1 (IGF-1) caused significant increase in [3H]thymidine incorporation, bromodeoxyuridine uptake, and increased CSMC number, with PDGF-BB (≥0.2 nM) substantially more effective than IGF-1. Surprisingly, CSMC lacked expression of PDGF receptor-β (PDGF-Rβ) upon isolation but by 4 days in vitro, CSMC gained expression of PDGF-Rβ as shown by quantitative PCR, Western blot analysis, and immunocytochemistry; these CSMC responded to PDGF-BB but not IGF-1. PDGF-BB caused PDGF-Rβ phosphorylation and mobilization from the surface membrane, leading to activation of both Akt and ERK signaling pathways, which were essential for subsequent proliferation. In contrast, PDGF-AA, FGF, EGF, and IGF-1 were ineffective. In vivo, control CSMC lacked expression of PDGF-Rβ. However, this changed rapidly with TNBS-colitis, and by day 2 when CSMC proliferation in vivo is maximal, freshly isolated CSMC showed on-going PDGF-Rβ phosphorylation that was further increased by exogenous PDGF-BB. This suggests that the onset of PDGF-Rβ expression is a key factor in CSMC growth in vitro and in vivo, where inflammation may damage intrinsic inhibitory mechanisms and thus lead to hyperplasia.

Purinergic and nitrergic neuromuscular transmission mediates spontaneous neuronal activity in the rat colon

2010 ◽  
Vol 299 (1) ◽  
pp. G158-G169 ◽  
Author(s):  
Víctor Gil ◽  
Diana Gallego ◽  
Laura Grasa ◽  
María Teresa Martín ◽  
Marcel Jiménez
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Neuronal Activity ◽  
Neuromuscular Transmission ◽  
Muscle Cells ◽  
Rat Colon ◽  
Spontaneous Motility ◽  
Spontaneous Neuronal Activity ◽  
Depolarized Smooth Muscle

Nitric oxide (NO) and ATP mediate smooth muscle relaxation in the gastrointestinal tract. However, the involvement of these neurotransmitters in spontaneous neuronal activity is unknown. The aim of the present work was to study spontaneous neuromuscular transmission in the rat midcolon. Microelectrode experiments were performed under constant stretch both in circular and longitudinal directions. Spontaneous inhibitory junction potentials (sIJP) were recorded. Tetrodotoxin (1 μM) and apamin (1 μM) depolarized smooth muscle cells and inhibited sIJP. Nω-nitro-l-arginine (l-NNA, 1 mM) depolarized smooth muscle cells but did not modify sIJP. In contrast, the P2Y1 antagonist MRS-2500 (1 μM) did not modify the resting membrane potential (RMP) but reduced sIJP (IC50 = 3.1 nM). Hexamethonium (200 μM), NF-023 (10 μM), and ondansetron (1 μM) did not modify RMP and sIJP. These results correlate with in vitro (muscle bath) and in vivo (strain gauges) data where l-NNA but not MRS-2500 induced a sustained increase of spontaneous motility. We concluded that, in the rat colon, inhibitory neurons regulate smooth muscle RMP and cause sIJP. In vitro, the release of inhibitory neurotransmitters is independent of nicotinic, P2X, and 5-hydroxytryptamine type 3 receptors. Neuronal NO causes a sustained smooth muscle hyperpolarization that is responsible for a constant inhibition of spontaneous motility. In contrast, ATP acting on P2Y1 receptors is responsible for sIJP but does not mediate inhibitory neural tone. ATP and NO have complementary physiological functions in the regulation of gastrointestinal motility.

Epicardial Cells of Human Adults Can Undergo an Epithelial-to-Mesenchymal Transition and Obtain Characteristics of Smooth Muscle Cells In Vitro

Stem Cells ◽  
2007 ◽  
Vol 25 (2) ◽  
pp. 271-278 ◽  
Author(s):  
John van Tuyn ◽  
Douwe E. Atsma ◽  
Elizabeth M. Winter ◽  
Ietje van der Velde-van Dijke ◽  
Daniel A. Pijnappels ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Muscle Cells ◽  
Mesenchymal Transition ◽  
Epicardial Cells ◽  
Human Adults

Characterization and confocal imaging of calponin in gastrointestinal smooth muscle

1993 ◽  
Vol 265 (5) ◽  
pp. C1371-C1378 ◽  
Author(s):  
M. P. Walsh ◽  
J. D. Carmichael ◽  
G. J. Kargacin
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Smooth Muscle Cells ◽  
Thin Filament ◽  
Muscle Cells ◽  
Biochemical Properties ◽  
Confocal Imaging ◽  
Isolated Cells ◽  
Independent Manner

Calponin isolated from chicken gizzard smooth muscle binds in vitro to actin in a Ca(2+)-independent manner and thereby inhibits the actin-activated Mg(2+)-adenosinetriphosphatase of smooth muscle myosin. This inhibition is relieved when calponin is phosphorylated by protein kinase C or Ca2+/calmodulin-dependent protein kinase II, suggesting that calponin is involved in thin filament-associated regulation of smooth muscle contraction. To further examine this possibility, calponin was isolated from toad stomach smooth muscle, characterized biochemically, and localized in intact isolated cells. Toad stomach calponin had the same basic biochemical properties as calponin from other sources. Confocal immunofluorescence microscopy revealed that calponin in intact smooth muscle cells was localized to long filamentous structures that were colabeled by antibodies to actin or tropomyosin. Preservation of the basic biochemical properties of calponin from species to species suggests that these properties are relevant for its in vivo function. Its colocalization with actin and tropomyosin indicates that calponin is associated with the thin filament in intact smooth muscle cells.

Light and dark smooth muscle cells in estrogen-stimulated rat myometrium

1976 ◽  
Vol 54 (6) ◽  
pp. 822-833 ◽  
Author(s):  
R. E. Garfield ◽  
E. E. Daniel
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Atp Depletion ◽  
Metabolic Inhibitors ◽  
Volume Control ◽  
Control Mechanisms ◽  
Dark Cells ◽  
Light Cells

Smooth muscle cells of different densities to transmission of electrons (termed light and dark cells) were found in rat myometrium examined in the electron microscope following fixation by immersion in glutaraldehyde. Light cells accounted for about 4% of the total population of cells. No light cells were found in tissues fixed in situ by intraarterial perfusion with glutaraldehyde. In addition to staining differences, light cells were distinguished from most dark cells by differences in nuclear, mitochondrial, endoplasmic reticular, and surface structures. The relative number of light and dark cells after in vitro fixation was not changed in tissues relaxed with adrenaline or contracted with oxytocin. Mechanical injury resulted in increased numbers of light cells. Similarly, chemical injury with metabolic inhibitors resulted in ATP depletion, followed by increased numbers of light cells and gain in water content. We concluded that light cells were produced by mechanical or metabolic damage, leading to loss of volume control mechanisms, swelling, and leakage of protein. Light cells found after fixation in vitro in numerous prior studies represent cells damaged during isolation, and not a physiological variant among smooth muscle cells.

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