Agonist-mediated activation of PLA2 initiates Ca2+ mobilization in intestinal longitudinal smooth muscle

1995 ◽  
Vol 269 (1) ◽  
pp. G93-G102 ◽  
Author(s):  
K. S. Murthy ◽  
J. F. Kuemmerle ◽  
G. M. Makhlouf
Keyword(s):  
Smooth Muscle ◽  
Longitudinal Muscle ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Cell Types ◽  
Initial Increase ◽  
Channel Blockers ◽  
Longitudinal Smooth Muscle ◽  
Highly Sensitive ◽  
Cyclic Adp Ribose

Recent studies have shown that Ca2+ mobilization in longitudinal muscle is initiated by inositol 1,4,5-trisphosphate (IP3)-independent Ca2+ influx that acts as a trigger for Ca(2+)-induced Ca2R release. The present study examined whether arachidonic acid (AA) acts as mediator of the initial Ca2+ influx. Cholecystokinin octapeptide caused transient concentration-dependent increase in AA release in dispersed intestinal longitudinal but not circular muscle cells followed by sustained increase in both muscle cell types. The initial increase in AA release coincided with the initial Ca2+ transient and muscle contraction: all three events were abolished by guanosine 5'-O-(2-thiodiphosphate), pertussis toxin (PTX), and the phospholipase A2 (PLA2) inhibitor, dimethyleicosadienoic acid, but were not affected by calphostin C or neomycin. Exogenous AA caused concentration-dependent contraction and increase in cytosolic free Ca2+ ([Ca2+]i) in longitudinal but not circular muscle cells; both events were abolished by Ca2+ channel blockers. Depletion of Ca2+ stores with thapsigargin attenuated with thapsigargin attenuated agonist- and AA-mediated increase in [Ca2+]i and contraction in longitudinal muscle cells: the residual [Ca2+]i increase (35%) and contraction (25%) reflected the component of Ca2+ influx. We conclude that AA released by agonist-mediated G protein-dependent PTX-sensitive activation of PLA2 mediates Ca2+ influx, which then triggers Ca(2+)-induced Ca2+ release. The process is independent of phosphatidylinositol hydrolysis and occurs exclusively in longitudinal smooth muscle, in which Ca2+ release channels are highly sensitive to Ca2+, ryanodine, and cyclic ADP-ribose and insensitive to IP3.

Agonist-activated, ryanodine-sensitive, IP3-insensitive Ca2+ release channels in longitudinal muscle of intestine

1994 ◽  
Vol 266 (5) ◽  
pp. C1421-C1431 ◽  
Author(s):  
J. F. Kuemmerle ◽  
K. S. Murthy ◽  
G. M. Makhlouf
Keyword(s):  
Longitudinal Muscle ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Cell Types ◽  
Ruthenium Red ◽  
Effective Concentration ◽  
Channel Blockers ◽  
Inositol 1,4,5 Trisphosphate ◽  
Dissociation Constant Kd ◽  
Ca2 Channels

We have previously shown that Ca2+ mobilization in longitudinal muscle is not mediated by inositol 1,4,5-trisphosphate (IP3) and depends on an obligatory influx of Ca2+. The present study examined whether Ca2+ influx activates ryanodine-sensitive Ca2+ channels to cause Ca(2+)-induced Ca2+ release. Ryanodine bound with high affinity to longitudinal muscle cells [dissociation constant (Kd) 7.3 +/- 0.3 nM] and microsomes (Kd 7.5 +/- 0.4 nM) and induced concentration-dependent 45Ca2+ efflux [50% effective concentration (EC50) 1.3 +/- 0.5 nM], increase in cytosolic free Ca2+ (EC50 2.0 +/- 0.7 nM), and contraction (EC50 0.9 +/- 0.2 nM) but had no effect in circular muscle cells. Ryanodine binding and ryanodine-induced Ca2+ release were enhanced by caffeine and inhibited by dantrolene and ruthenium red but were not affected by IP3 or heparin. Changes in Ca2+ concentration (50-500 nM) caused Ca2+ release from permeabilized longitudinal but not circular muscle cells loaded with 45Ca2+. The contractile agonist cholecystokinin-8 elicited 45Ca2+ efflux in both circular and longitudinal muscle cells; efflux in longitudinal muscle cells was abolished by Ca2+ channel blockers and by pretreatment of the cells with ryanodine. Pretreatment with thapsigargin abolished agonist-induced 45Ca2+ efflux in both cell types. We conclude that ryanodine-sensitive IP3-insensitive Ca2+ release channels with properties similar to those in cardiac muscle are present in longitudinal but not circular muscle cells of intestine and that agonist-mediated Ca2+ influx activates these channels, leading to Ca(2+)-induced Ca2+ release.

The Morphology of the Gut of the Brown Trout (Salmo trutta)

1959 ◽  
Vol s3-100 (50) ◽  
pp. 183-198
Author(s):  
G. BURNSTOCK
Keyword(s):  
Smooth Muscle ◽  
Salmo Trutta ◽  
Longitudinal Muscle ◽  
Circular Muscle ◽  
Living System ◽  
Cardiac Stomach ◽  
Longitudinal Smooth Muscle ◽  
Brown Trout Salmo Trutta ◽  
Pyloric Stomach ◽  
Longitudinal Layer

1. In the trout gut a short oesophagus containing only striated circular muscles opens into a large cardiac stomach possessing inner circular and outer longitudinal smooth muscle-coats, as well as a musculsris mucosse. Ahout 45 pyloric caeca come off the intestine, which, while containing muscle-coats, does not possess a muscularis mucosae. In the rectum, the longitudinal muscle is as thick as the circular muscle-coat, hut in other regions the circular muscle is dominant, especially in the pyloric stomach where it is over 10 times as thick ss the longitudinal layer. 2. The mucosa is distinguished by the presence of a prominent layer of dense collagen, the stratum compactum, which is perforated only by nerves and blood-vessels. This layer forms a firm and relatively inextensible (approximately 10% extensibility) basis to the gut-wall. It limits the extensibility of the smooth muscle to 75% radially in the stomach and 25% radially and longitudinally in the intestine. In contrast, the stomachs of the pike and perch, which do not possess a stratum compactum, extend up so 200%. 3. A detailed description of the regional junctions and sphincters gives a basis for the interpretation of events occurring in the living system. Valves at the junction of the pneumatic duct with the oesophagus, and between the duodenum and pyloric stomach, serve to prevent the regurgitation of gas and semi-digested food respectively. A complex sphincter mechanism exists at the pylorus, and to a lesser extent at the antrum. A series of about five circular muscle-constrictors represents the anus. 4. It is suggested that the cells forming the stratum granulosum, a layer closely associated with the stratum compactum, are composed of active fibroblast cells producing collagen. 5. The rectum contains a muscular annulo-spiral septum of unknown function which protrudes into the lumen.

Role of HERG-like K+ currents in opossum esophageal circular smooth muscle

1999 ◽  
Vol 277 (6) ◽  
pp. C1284-C1290 ◽  
Author(s):  
Hamid I. Akbarali ◽  
Hemant Thatte ◽  
Xue Dao He ◽  
Wayne R. Giles ◽  
Raj K. Goyal
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Smooth Muscle Cells ◽  
Single Cells ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Resting Membrane Potential ◽  
Channel Blockers ◽  
Circular Smooth Muscle ◽  
Inward Currents

An inwardly rectifying K+ conductance closely resembling the human ether-a-go-go-related gene (HERG) current was identified in single smooth muscle cells of opossum esophageal circular muscle. When cells were voltage clamped at 0 mV, in isotonic K+ solution (140 mM), step hyperpolarizations to −120 mV in 10-mV increments resulted in large inward currents that activated rapidly and then declined slowly (inactivated) during the test pulse in a time- and voltage- dependent fashion. The HERG K+ channel blockers E-4031 (1 μM), cisapride (1 μM), and La3+ (100 μM) strongly inhibited these currents as did millimolar concentrations of Ba2+. Immunoflourescence staining with anti-HERG antibody in single cells resulted in punctate staining at the sarcolemma. At membrane potentials near the resting membrane potential (−50 to −70 mV), this K+ conductance did not inactivate completely. In conventional microelectrode recordings, both E-4031 and cisapride depolarized tissue strips by 10 mV and also induced phasic contractions. In combination, these results provide direct experimental evidence for expression of HERG-like K+ currents in gastrointestinal smooth muscle cells and suggest that HERG plays an important role in modulating the resting membrane potential.

scholarly journals Rhythmic Electrical Activity in Stomach and Intestine of Toad

1980 ◽  
Vol 86 (1) ◽  
pp. 237-248
Author(s):  
ALLEN MANGEL ◽  
C. LADD PROSSER
Keyword(s):  
Smooth Muscle ◽  
Longitudinal Muscle ◽  
Circular Muscle ◽  
Sodium Concentration ◽  
Muscle Layer ◽  
Free Solution ◽  
Longitudinal Muscle Layer ◽  
Longitudinal Smooth Muscle ◽  
Mammalian Intestine ◽  
Periodic Changes

The intact stomach of the toad initiates rhythmic slow-spikes of 5–15 s duration and frequency of 3-5 min−1. The spontaneous electrical waves originate in the longitudinal muscle layer; isolated circular muscle is quiescent. Aboral conduction velocity is 0.12–0.9 mm s−1. Reduction of external sodium concentration from 89.5 to 15 mM produced no effect on slow spikes, although further reduction to 1.5 mM increased frequency and decreased amplitude. Slow-spikes were unaffected by ouabain or by incubation in potassium-free solution. When calcium in the medium was reduced, slow-spike amplitude and frequency decreased. Slow-spikes exhibited a change in amplitude of 16 mV per decade change in CaO2+; slow-spikes were eliminated at 10−8 M CaO2+ and by blockers of calcium conductance channels. Intact intestine of toad demonstrated slow-waves which resembled those of mammalian intestine. These were sensitive to changes in external sodium and were eliminated by 1 × 10−4M ouabain. It is suggested that rhythmic slow-spikes of longitudinal smooth muscle of amphibian stomach may result from periodic changes in Ca conductance whereas endogenous electrical waves of intestine may result from rhythmic extrusion of sodium.

β3-Adrenoceptors: relaxant function and mRNA detection in smooth muscle cells isolated from the human colon

2004 ◽  
Vol 82 (7) ◽  
pp. 515-522 ◽  
Author(s):  
Carola Severi ◽  
Ivan Tattoli ◽  
Giovanna Romano ◽  
Vito D Corleto ◽  
Gianfranco Delle Fave
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Human Colon ◽  
Cell Types ◽  
Intrinsic Activity ◽  
Dependent Manner ◽  
Taenia Coli ◽  
Circular Smooth Muscle

Functional involvement of β3-adrenoceptors in controlling human gastrointestinal motility has not been unequivocally assessed yet. The direct myogenic contribution of these receptors was examined, by in vitro functional studies and analysis of mRNA expression, on smooth muscle cells separately isolated from taenia coli and circular muscle layers of the human colon. Isoproterenol, a nonselective β-adrenoceptor agonist, relaxed, in a concentration-dependent manner, both human taenia coli and circular colonic smooth muscle cells, although displaying a higher intrinsic activity (65.3 ± 2.3 vs. 55.2 ± 1.4% maximal relaxation) and potency (pEC50: 7.41 ± 0.07 vs. 6.32 ± 0.08) were greater on taenia coli than circular cells. In the presence of the β1-antagonist CGP20712A and of the β2-antagonist ICI 118,551, a 25–30% decrease in isoproterenol intrinsic activity was observed on both cell types and on taenia coli, the nonselective β1/β2-antagonist propranolol produced a rightward shift of the isoproterenol concentration-response curve with mean estimated pKB values (8.12 ± 0.27 at 0.1 µM and 6.45 ± 0.13 at 1 µM) lower than that expected for both β1- and β2-adrenoceptors. CGP12177A and SR 58611A, two β3-adrenoceptor agonists, presented an intrinsic activity comparable to that of isoproterenol in the presence of β1- and β2-antagonists, the former being more potent on taenia coli than on circular smooth muscle cells. β3-Adrenoceptor mRNA was detected by reverse transcription PCR on both cell types. These results strongly suggest a direct functional role of β3-adrenoceptors in the human colon.Key words: adrenoceptors, β3-adrenoceptors, smooth muscle cells, taenia coli, human colon.

Intercellular metabolic coupling in canine colon musculature

1995 ◽  
Vol 268 (6) ◽  
pp. C1492-C1502 ◽  
Author(s):  
L. Farraway ◽  
A. K. Ball ◽  
J. D. Huizinga
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Gap Junctions ◽  
Longitudinal Muscle ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Muscle Layer ◽  
Circular Smooth Muscle ◽  
Metabolic Coupling ◽  
Cells Of Cajal

Intercellular communication within the musculature of the canine colon was studied by examining the results of neurobiotin diffusion after injection of the tracer into smooth muscle cells at different locations within the muscle layer. Circular muscle at the submucosal surface, circular muscle adjacent to the myenteric plexus, and longitudinal muscle demonstrated different degrees of time-dependent tracer spread. At the submucosal surface, tracer spread was rapid, extensive, and unimpeded by connective tissue septa. At the myenteric side, tracer spread was also extensive but was much slower and confined to bundles of cells bordered by septa. In contrast to previous studies that suggest an absence of gap junctions at the myenteric side of the circular muscle, the neurobiotin spread indicates full metabolic coupling of all circular smooth muscle cells. Furthermore, in contrast to the belief that longitudinal muscle is completely devoid of gap junctions, tracer spread occurred between cells in this layer, although neurobiotin diffusion was very limited, nonuniform, and slow. In each area of the musculature studied, tracer spread was inhibited by octanol. When very long injection and wait times were implemented at the submucosal surface of the circular muscle, neurobiotin was observed to cross septa through the network of interstitial cells of Cajal, indicating that it is this network that provides communication between lamellae.

Excitatory and inhibitory responses of Oddi's sphincter in guinea pigs

1991 ◽  
Vol 260 (4) ◽  
pp. G615-G624 ◽  
Author(s):  
T. Hirose ◽  
Y. Ito
Keyword(s):  
Smooth Muscle ◽  
Action Potentials ◽  
Regional Differences ◽  
Longitudinal Muscle ◽  
Smooth Muscles ◽  
Central Area ◽  
Circular Muscle ◽  
Electrical Field Stimulation ◽  
Muscle Cells ◽  
Field Stimulation

We examined the intrinsic motor innervation of the guinea pig choledochoduodenal junction and actions of cholecystokinin octapeptide (CCK-OP) on contractile and membrane activity of circular and longitudinal smooth muscles from three different areas: close to the choledochal sphincter (I); central area in the ampulla (II); and close to the duodenal papilla (III). In response to electrical field stimulation, circular muscle strips showed an initial twitchlike contraction followed by relaxation in areas I and II and only a transient relaxation in the muscle strips prepared from area III. In the longitudinal strips, the regional differences in response to the field stimulation were not prominent, and biphasic twitchlike contractions were observed in areas I, II, and III. Electric field stimulation evoked excitatory junction potentials (EJPs), inhibitory junction potentials (IJPs), or biphasic membrane response (initial EJP followed by an IJP) in the circular and longitudinal smooth muscle cells. Prominent regional differences were observed in areas I, II, and III. Namely, in area III both the circular and longitudinal muscle layers IJPs predominated, whereas in area I the response was predominantly excitatory. CCK-OP (greater than 10-8M) evoked repetitive action potentials in the circular muscle cells, and CCK-OP increased the frequency of slow waves or the spontaneous action potentials in longitudinal muscle cells. CCK-OP enhanced the amplitude of the IJPs and EJPs in both muscle layers. It would thus appear that bile flow is controlled by complex combinations of contraction and relaxation of the smooth muscle that may be due to regional differences in excitatory and inhibitory innervations.

scholarly journals Jun kinase-induced overexpression of leukemia-associated Rho GEF (LARG) mediates sustained hypercontraction of longitudinal smooth muscle in inflammation

2014 ◽  
Vol 306 (12) ◽  
pp. C1129-C1141 ◽  
Author(s):  
Othman Al-Shboul ◽  
Ancy D. Nalli ◽  
Divya P. Kumar ◽  
Ruizhe Zhou ◽  
Sunila Mahavadi ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Contraction ◽  
Longitudinal Muscle ◽  
Rho Kinase ◽  
Muscle Cells ◽  
Circular Smooth Muscle ◽  
Jun Kinase ◽  
Longitudinal Smooth Muscle ◽  
Tnf Α

The signaling pathways mediating sustained contraction of mouse colonic longitudinal smooth muscle and the mechanisms involved in hypercontractility of this muscle layer in response to cytokines and TNBS-induced colitis have not been fully explored. In control longitudinal smooth muscle cells, ACh acting via m3 receptors activated sequentially Gα12, RhoGEF (LARG), and the RhoA/Rho kinase pathway. There was abundant expression of MYPT1, minimal expression of CPI-17, and a notable absence of a PKC/CPI-17 pathway. LARG expression was increased in longitudinal muscle cells isolated from muscle strips cultured for 24 h with IL-1β or TNF-α or obtained from the colon of TNBS-treated mice. The increase in LARG expression was accompanied by a significant increase in ACh-stimulated Rho kinase and ZIP kinase activities, and sustained muscle contraction. The increase in LARG expression, Rho kinase and ZIP kinase activities, and sustained muscle contraction was abolished in cells pretreated with the Jun kinase inhibitor, SP600125 . Expression of the MLCP activator, telokin, and MLCP activity were also decreased in longitudinal muscle cells from TNBS-treated mice or from strips treated with IL-1β or TNF-α. In contrast, previous studies had shown that sustained contraction in circular smooth muscle is mediated by sequential activation of Gα13, p115RhoGEF, and dual RhoA-dependent pathways involving phosphorylation of MYPT1 and CPI-17. In colonic circular smooth muscle cells isolated from TNBS-treated mice or from strips treated with IL-1β or TNF-α, CPI-17 expression and sustained muscle contraction were decreased. The disparate changes in the two muscle layers contribute to intestinal dysmotility during inflammation.

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.

Canine colonic circular muscle generates action potentials without the pacemaker component

1994 ◽  
Vol 72 (1) ◽  
pp. 70-81 ◽  
Author(s):  
Louis W. C. Liu ◽  
Jan D. Huizinga
Keyword(s):  
Smooth Muscle ◽  
Calcium Channel ◽  
Action Potentials ◽  
Interstitial Cells Of Cajal ◽  
Longitudinal Muscle ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Interstitial Cells ◽  
Slow Waves ◽  
Cells Of Cajal

Two dominant types of action potentials in canine colon are slow wave type action potentials (slow waves) and spike-like action potentials (SLAPs). The slow waves, originating at the submuscular surface where a network of interstitial cells of Cajal (ICCs) is found, possess a pacemaker component. Activation of the pacemaker component is insensitive to voltage changes and L-type calcium channel blockers, and is postulated to involve a metabolic clock sensitive to cyclic AMP. SLAPs are more prominent in the longitudinal muscle. To understand the contribution circular muscle cells make to the generation of these action potentials, a circular muscle preparation (devoid of the submuscular ICC – smooth muscle network, longitudinal muscle, and myenteric plexus) was developed. Circular muscle preparations were spontaneously quiescent, with a resting membrane potential of −62.9 ± 0.6 mV. Ba2+ (0.5 mM) depolarized the cells to −51.8 ± 0.6 mV and induced electrical oscillations with a frequency, duration, amplitude, and rate of rise equal to 6.6 ± 0.4 cpm, 2.2 ± 0.2 s, 19.4 ± 0.9 mV, and 21.8 ± 1.7 mV/s, respectively. In most cases, Ba2+-induced oscillations were preceded by a prepotential of 4.4 ± 0.3 mV, with a rate of rise of 1.1 ± 0.1 mV/s. Ba2+-induced oscillations were abolished by 1 μM D600 as well as by repolarization of 6–12 mV. Addition of 0.1 μM Bay K8644 in the presence of Ba2+ further depolarized circular muscle cells to −42.4 ± 0.8 mV and increased the oscillation frequency to 16.8 ± 1.8 cpm. The electrical oscillations induced in circular muscle preparations by Ba2+ and Bay K8644 were similar to the SLAPs exhibited by the isolated longitudinal muscle layer, indicating that generation of SLAPs is an intrinsic property of smooth muscle cells. Forskolin (1 μM), previously shown to dramatically decrease the frequency but not the amplitude of slow waves in preparations including the submuscular ICC network, decreased the amplitude of the Ba2+-induced oscillations in circular muscle preparations without changing the frequency. These results provide strong evidence for the hypothesis that the submuscular ICC – smooth muscle network is essential for the initiation of the pacemaker component of the colonic slow waves. The mechanism for regulating the frequency of slow waves is different from that responsible for the Ba2+-induced oscillations in circular muscle preparations. Circular muscle cells are shown to be excitable and capable of generating oscillatory activity dominated by L-type calcium channel activity, which is regulated by K+ conductance.Key words: interstitial cells of Cajal, smooth muscle, dog colon, barium chloride, potassium conductance, Bay K8644, pacemaking activity.

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