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At least 811 records · Page 45Linked to original sources
PubMed1994

Angiotensin II up-regulates the expression of type A endothelin receptor in human vascular smooth muscle cells.

Using vascular smooth muscle cells, the effect of angiotensin II on endothelin receptor regulation was examined. Vascular smooth muscle cells cultivated from human pulmonary artery exhibited high affinity receptors for endothelin-1. When the cells were exposed to angiotensin II, the number of receptors was found to be increased without any change in their affinity. The ligand binding was effectively displaced by BQ123, a selective antagonist for type A endothelin receptor, but not by S6c, a selective ligand for type B receptor, in both control and angiotensin II-treated cells. The level of mRNA coding for the type A receptor was elevated in the latter. These results indicate that angiotensin II up-regulates type A endothelin receptors in human vascular smooth muscle cells through an increase in their corresponding mRNA, suggesting a link between the renin-angiotensin and the endothelin systems.

Angiotensin II↗
PubMed2004

The role of RhoA-mediated Ca2+ sensitization of bronchial smooth muscle contraction in airway hyperresponsiveness.

Smooth muscle contraction is mediated by Ca2+-dependent and Ca2+-independent pathways. The latter Ca2+-independent pathway, termed Ca2+ sensitization, is mainly regulated by a monomeric GTP binding protein RhoA and its downstream target Rho-kinase. Recent studies suggest a possible involvement of augmented RhoA/Rho-kinase signaling in the elevated smooth muscle contraction in several human diseases. An increased bronchial smooth muscle contractility, which might be a major cause of the airway hyperresponsiveness that is a characteristic feature of asthmatics, has also been reported in bronchial asthma. Here, we will discuss the role of RhoA/Rho-kinase-mediated Ca2+ sensitization of bronchial smooth muscle contraction in the pathogenesis of airway hyperresponsiveness. Agonist-induced Ca2+ sensitization is also inherent in bronchial smooth muscle. Since the Ca2+ sensitization is sensitive to a RhoA inactivator, C3 exoenzyme, and a Rho-kinase inhibitor, Y-27632, the RhoA/Rho-kinase pathway is involved in the signaling. It is of interest that the RhoA/Rho-kinase-mediated Ca2+ sensitization of bronchial smooth muscle contraction is markedly augmented in experimental asthma. Moreover, Y-27632 relaxes the bronchospasm induced by contractile agonists and antigens in vivo. Y-27632 also has an ability to inhibit airway hyperresponsiveness induced by antigen challenge. Thus, the RhoA/Rho-kinase pathway might be a potential target for the development of new treatments for asthma, especially in airway hyperresponsiveness.

Animals↗
PubMed2003

Expression of transcription factors and matrix genes in response to serum stimulus in vascular smooth muscle cells.

During atherogenesis vascular smooth muscle cells are converted from a contractile into a synthetic phenotype characterized by enhanced matrix production. The transcription factors Gax and GATA-6 are considered negative, and Oct-1 positive regulators of the synthetic phenotype. Since the phenotype transition can be induced by culturing the cells with serum, we followed the expression of Gax, GATA-6 and Oct-1, integrins and matrix genes in quiescent porcine vascular smooth muscle cells after serum application. Comparisons were made between enzymatically released primary smooth muscle cells and cells grown out from explants of the medial layer of porcine aorta. The serum-mediated down-regulation of Gax was more intense than that of GATA-6, and stronger in explant-derived than in primary cells. Serum was without influence on the expression of Oct-1. Changes in the expression of the transcription factors preceded the induction of integrin alpha2 and the down-regulation of decorin, while mRNAs for laminin beta1 and osteopontin rose immediately after serum stimulation. Primary cells reacted more rapidly than explant cells with respect to changes in laminin isoforms. Studies with a Gax-expressing adenovirus indicated that among all the gene products tested only the expression of integrin alpha2 responded to Gax induction. Thus, our data show that i) Gax should be considered a transcription factor being directly responsible for only few aspects of the phenotypic conversion of smooth muscle cells and that ii) explant cells may represent a subpopulation of smooth muscle cells, which differ from the total population of smooth muscle cells, as obtained in primary culture, in their response to serum stimuli.

Adenoviridae↗
PubMed1994

Embryonic chicken gizzard: smooth muscle and non-muscle myosin isoforms.

Antibodies to smooth muscle and non-muscle myosin allow the development of smooth muscle and its capillary system in the embryonic chicken gizzard to be followed by immunofluorescent techniques. Although smooth muscle development proceeds in a serosal to luminal direction, angiogenetic cell clusters develop independently at the luminal side close to the epithelial layer, and the presumptive capillaries invade the developing muscle in a luminal to serosal direction. The smooth muscle and non-muscle myosin heavy chains in this avian system cannot be separated by SDS polyacrylamide gel electrophoresis and do not show isoform specificity in immunoblotting, unlike the system found in mammals. Only two myosin heavy chains with M(r) of 200 and 196 kDa were separable and considerable immunological cross-reactivity was found between the denatured myosin isoform heavy chains.

Animals↗
PubMed1983

Effects of calcium and verapamil on vesicourethral smooth muscle of rabbits.

Isolated smooth muscle strips from the rabbit bladder body, bladder base, and proximal urethra were contracted with ionic calcium (Ca2+) alone and with the calcium-selective ionophore A23187, acetylcholine, norepinephrine, adenosine triphosphate (ATP), and direct electrical stimulation. The effects of Ca2+ and the calcium entry blocker verapamil on spontaneous muscle activity and on contractions induced by these agonists were examined. Ca2+ -free Tyrode's solution and verapamil, 1 x 10(-7)M and above, relaxed all of the vesicourethral smooth muscle strips. In addition verapamil, 1 x 10(-8) to 1 x 10(-6) M depending on the particular stimulant employed, noncompetitively inhibited smooth muscle contractions elicited by Ca2+, acetylcholine, norepinephrine, ATP, and direct electrical stimulation. It was concluded that transmembrane Ca2+ influx was important not only in the maintenance of tone and spontaneous phasic muscle activity, but also for the activation of contractions induced by all of the stimulants tested. The data also suggest that intracellular Ca2+ fraction(s) participate in the contractile responses to acetylcholine and norepinephrine challenge, but not to contractions evoked by ATP or electricity.

Acetylcholine↗
PubMed2006

Physiological roles of ATP-sensitive K+ channels in smooth muscle.

Potassium channels that are inhibited by intracellular ATP (ATP(i)) were first identified in ventricular myocytes, and are referred to as ATP-sensitive K+ channels (i.e. K(ATP) channels). Subsequently, K+ channels with similar characteristics have been demonstrated in many other tissues (pancreatic beta-cells, skeletal muscle, central neurones, smooth muscle). Approximately one decade ago, K(ATP) channels were cloned and were found to be composed of at least two subunits: an inwardly rectifying K+ channel six family (Kir6.x) that forms the ion conducting pore and a modulatory sulphonylurea receptor (SUR) that accounts for several pharmacological properties. Various types of native K(ATP) channels have been identified in a number of visceral and vascular smooth muscles in single-channel recordings. However, little attention has been paid to the molecular properties of the subunits in K(ATP) channels and it is important to determine the relative expression of K(ATP) channel components which give rise to native K(ATP) channels in smooth muscle. The aim of this review is to briefly discuss the current knowledge available for K(ATP) channels with the main interest in the molecular basis of native K(ATP) channels, and to discuss their possible linkage with physiological functions in smooth muscle.

Adenosine Triphosphate↗
PubMed2002

Mechanisms of reactivity of urinary bladder smooth muscle.

BACKGROUND: Mechanism of bladder smooth muscle contraction and relaxation and its pharmacological influence in various pathologic states are of incremental interest of investigators and clinicians. OBJECTIVES: The aim of our study was to assess the reactivity of urinary bladder smooth muscle in guinea pigs to two different pharmacological agents. METHODS: We compared the in vitro reactivity of smooth muscle strips of guinea pig urinary bladder to muscarinic stimulation by carbachol and acetylcholine. We prepared two kinds of strips, urothelium-denuded and with intact urothelium. Both kinds of strips were aerated under tension in Krebs-Henseleit's solution in organ-bath for 1 hour and after that cumulative concentration-response curves to carbachol (10(-9) - 10(-5) mol/l) and acetylcholine (10(-8) - 10(-3) mol/l) were constructed. RESULTS: We observed significantly higher reactivity of smooth muscle strips to carbachol, comparing to acetylcholine at the same concentrations both in strips with urothelium (at concentration 10(-5) mol/l: 22.1 g/100 mg vs 6.1 g/100 mg) and in urothelium-denuded strips (at concentration 10(-5) mol/l: 24.5 g/100 mg vs 5.1 g/100 mg). The reactivity differences between strips with and without urothelium were not significant, however, in higher concentrations of acetylcholine (10(-4) and 10(-5) mol/l) and carbachol (10(-6) and 10(-5) mol/l) we noticed no significant inhibition of contractile response of smooth muscle strips with intact urothelium. CONCLUSION: In our experiments we confirmed that carbachol was more potent constrictor than acetylcholine in detrusor smooth muscle strips of guinea pigs. The presence of urothelium did not change the reactivity significantly. (Fig. 4, Ref: 23.).

Acetylcholine↗
PubMed1987

Analysis of the glycopeptides derived from the extracellular matrix secreted by cultured bovine aortic smooth muscle cells.

Modulation of smooth muscle cell behaviour in culture has been associated with changes in the extracellular matrix. In the present study cultures of bovine aortic smooth muscle cells were compared in the rapidly proliferating and confluent phases of growth. The extracellular matrix was similar in both phases of growth and consisted of glycoproteins ranging from molecular weight 20,000 to over 200,000. The glycopeptides derived from these components displayed several differences. N-linked heteropolysaccharides of the biantennary and complex (more than two branches) types were predominant in the matrix of the confluent phase. Larger amounts of high mannose glycopeptides were present in the preparations from proliferating cells. O-Glycosidic glycopeptides were minor components in both preparations, but a slight increase was noted in the confluent phase of growth. Some of the changes in glycopeptides were interpreted in terms of the levels of the major components of the matrix such as the interstitial procollagens and fibronectin. The results indicate that processing of oligosaccharides associated with secreted glycoproteins of the extracellular matrix correlates with the state of growth of smooth muscle cells in culture.

Animals↗
PubMed2004

Anesthetics inhibit acetylcholine-promoted guanine nucleotide exchange of heterotrimeric G proteins of airway smooth muscle.

BACKGROUND: Anesthetics inhibit airway smooth muscle contraction in part by a direct effect on the smooth muscle cell. This study tested the hypothesis that the anesthetics halothane and hexanol, which both relax airway smooth muscle in vitro, inhibit acetylcholine-promoted nucleotide exchange at the alpha subunit of the Gq/11 heterotrimeric G protein (Galphaq/11; i.e., they inhibit muscarinic receptor-Galphaq/11 coupling). METHODS: The effect of halothane (0.38 +/- 0.02 mm) and hexanol (10 mm) on basal and acetylcholine-stimulated Galphaq/11 guanosine nucleotide exchange was determined in membranes prepared from porcine tracheal smooth muscle. The nonhydrolyzable, radioactive form of guanosine-5'-triphosphate, [S]GTPgammaS, was used as the reporter for Galphaq/11 subunit dissociation from the membrane to soluble fraction, which was immunoprecipitated with rabbit polyclonal anti-Galphaq/11 antiserum. RESULTS: Acetylcholine caused a significant time- and concentration-dependent increase in the magnitude of Galphaq/11 nucleotide exchange compared with basal values (i.e., without acetylcholine), reaching a maximal difference at 100 microm (35.9 +/-2.9 vs. 9.8 +/-1.2 fmol/mg protein, respectively). Whereas neither anesthetic had an effect on basal Galphaq/11 nucleotide exchange, both halothane and hexanol significantly inhibited the increase in Galphaq/11 nucleotide exchange produced by 30 microm acetylcholine (by 59% and 68%, respectively). CONCLUSIONS: Halothane and hexanol interact with the receptor-heterotrimeric G-protein complex in a manner that prevents acetylcholine-promoted exchange of guanosine-5(')-triphosphate for guanosine-5'-diphosphate at Galphaq/11. These data are consistent with the ability of anesthetics to interfere with cellular processes mediated by heterotrimeric G proteins in many cells, including effects on muscarinic receptor-G-protein regulation of airway smooth muscle contraction.

Acetylcholine↗
PubMed1993

Cyclosporine A induces endothelin-1 release from cultured rat vascular smooth muscle cells.

Since vascular smooth muscle cells in culture are capable of secreting endothelin-1 (ET-1), we investigated the effect of cyclosporine A on ET-1 release from rat vascular smooth muscle cells. Cyclosporine A 10 microM significantly (P < 0.05) enhanced the secretion of ET-1 at 2, 8, 24 and 48 h (6.5 +/- 0.5, 11 +/- 0.7, 19 +/- 0.5, 37 +/- 1.6 fmol/10(6) cells, respectively) compared with vehicle (4.7 +/- 0.3, 8.1 +/- 0.6, 15 +/- 0.4, 27 +/- 2.0 fmol/10(6) cells, respectively). The cyclosporine-induced synthesis of ET-1 by vascular smooth muscle cell may participate in the pathogenesis of cyclosporine-induced vasoconstriction and vasculopathy via an autocrine regulatory mechanism.

Animals↗
PubMed2004

Properties of a tonically active, sodium-permeable current in mouse urinary bladder smooth muscle.

Urinary bladder smooth muscle (UBSM) elicits depolarizing action potentials, which underlie contractile events of the urinary bladder. The resting membrane potential of UBSM is approximately -40 mV and is critical for action potential generation, with hyperpolarization reducing action potential frequency. We hypothesized that a tonic, depolarizing conductance was present in UBSM, functioning to maintain the membrane potential significantly positive to the equilibrium potential for K(+) (E(K); -85 mV) and thereby facilitate action potentials. Under conditions eliminating the contribution of K(+) and voltage-dependent Ca(2+) channels, and with a clear separation of cation- and Cl(-)-selective conductances, we identified a novel background conductance (I(cat)) in mouse UBSM cells. I(cat) was mediated predominantly by the influx of Na(+), although a small inward Ca(2+) current was detectable with Ca(2+) as the sole cation in the bathing solution. Extracellular Ca(2+), Mg(2+), and Gd(3+) blocked I(cat) in a voltage-dependent manner, with K(i) values at -40 mV of 115, 133, and 1.3 microM, respectively. Although UBSM I(cat) is extensively blocked by physiological extracellular Ca(2+) and Mg(2+), a tonic, depolarizing I(cat) was detected at -40 mV. In addition, inhibition of I(cat) demonstrated a hyperpolarization of the UBSM membrane potential and decreased the amplitude of phasic contractions of isolated UBSM strips. We suggest that I(cat) contributes tonically to the depolarization of the UBSM resting membrane potential, facilitating action potential generation and thereby a maintenance of urinary bladder tone.

Action Potentials↗
PubMed2006

T-type Ca2+ channels in vascular smooth muscle: multiple functions.

Vascular smooth muscle is a major constituent of the blood vessel wall, and its many functions depend on type and location of the vessel, developmental or pathological state, and environmental and chemical factors. Vascular smooth muscle cells (VSMCs) use calcium as a signal molecule for multiple functions. An important component of calcium signaling pathways is the entry of extracellular calcium via voltage-gated Ca2+ channels, which in vascular smooth muscle cells (VSMCs) are of two main types, the high voltage-activated (HVA) L-type and low voltage-activated (LVA) T-type channels. Whereas L-type channels function primarily to regulate Ca2+ entry for contraction, it is generally accepted that T-type Ca2+ channels do not contribute significantly to arterial vasoconstriction, with the possible exception of the renal microcirculation. T-type Ca2+ channels are also present in some veins that display spontaneous contractile activity, where they likely generate pacemaker activity. T-type Ca2+ channel expression has also been associated with normal and pathological proliferation of VSMCs, often stimulated by external cues in response to insult or injury. Expression of T-type channels has been linked to the G1 and S phases of the cell cycle, a period important for the signaling of gene expression necessary for cell growth, progression of the cell cycle and ultimately cell division. To better understand T-type Ca2+ channel functions in VSM, it will be necessary to develop new approaches that are specifically targeted to this class of Ca2+ channels and its individual members.

Animals↗
PubMed1987

Influence of ATP, ADP and AMPPNP on the energetics of contraction in skinned smooth muscle.

The contraction of smooth muscle is influenced by the substrate MgATP and the product MgADP. The effects on force, shortening velocity and ATP-turnover, are consistent with an influence on the kinetics of cross-bridge cycling. Part of these effects are mediated via an influence on the regulation of contraction by myosin light chain phosphorylation. Results from preparations activated by thiophosphorylation, show that MgATP and MgADP also interact directly at the cross-bridge level, and are consistent with MgADP acting as a competitive ATP-analogue. The slow shortening velocity and decreased rate of ATP-induced relaxation from rigor in the presence of MgADP, suggest an inhibition of cross-bridge detachment. The rate of ATP-turnover was decreased in the presence of the nonhydrolyzable ATP-analogue AMPPNP. These results may contribute to the characterization of the biochemical reactions in the structurally organized smooth muscle contractile system. In addition, the influence of MgATP and MgADP on smooth muscle contraction suggest that the concentrations of substrate and products, at the level of the contractile proteins, may constitute important regulatory factors in vivo under conditions, such as hypoxia and ischemia, associated with impaired cellular energy supply.

Adenine Nucleotides↗
PubMed1997

Morphological and pharmacological characterization of guinea-pig prostatic smooth muscle cells in vitro.

BACKGROUND: Prostatic smooth muscle is thought to play a major role in the pathogenesis of bladder outlet obstruction in patients with benign prostatic hypertrophy. However, the physiology of prostatic smooth muscle cells remains largely unknown, in part due to the lack of a suitable model system. We therefore sought to establish an in vitro culture of guinea pig prostatic smooth muscle cells. METHODS: Immature guinea pig prostate was treated by enzymatic digestion and the cells obtained were used to initiate the primary culture. After 3 to 4 passages, cultured smooth muscle cells were examined morphologically by immunocytochemistry and electron microscopy. The contractile properties of cultured smooth muscle cells were also examined. RESULTS: The cultured prostatic cells demonstrated hill and valley morphology, which is a hallmark of smooth muscle cells in vitro, and stained positively for desmin. In addition, electron microscopic examination of ultrastructural morphology revealed myofilaments. Confluent cultures of prostatic smooth muscle cells showed a clear, dose-dependent contractile response to phenylephrine. Furthermore, contraction of the prostatic smooth muscle cells by 10(-6) mol/L phenylephrine was completely inhibited by pretreatment with 10(-6) mol/L terazosin. CONCLUSIONS: An in vitro culture of prostatic smooth muscle cells was established. This culture is likely to provide a powerful tool for elucidating the physiology and pathophysiology of prostatic smooth muscle.

Adrenergic alpha-Agonists↗
PubMed1991

Scanning electron microscopy of normal and vasospastic monkey cerebrovascular smooth muscle cells.

Normal cytoarchitecture of smooth muscle cells of monkey cerebral arteries was studied using scanning electron microscopy after removal of adventitial connective tissue by hydrolysis with HCl. Cerebral arteries were also examined after contraction in vitro with prostaglandin F2 alpha (PGF2 alpha). Anterior cerebral arteries were studied after exposure for 6 days in vivo to whole blood, oxyhemoglobin, methemoglobin, bilirubin, mock cerebrospinal fluid, or supernatant fluid from an incubated mixture of autologous blood and mock cerebrospinal fluid. Normal smooth muscle cells were spindle-shaped and oriented circumferentially around the vessel. They were often grouped into bundles of 5 to 10 cells; bundles were recognizable because cells within them were joined by multiple intercellular contacts. Groups of smooth muscle cells oriented longitudinally were present outside the circular layers of cells. The adventitial surface of muscle cells was smooth apart from fine longitudinal striations in some areas. Arteries contracted with PGF2 alpha had markedly convoluted and folded cell membranes. Muscle cells of vasospastic arteries and of arteries exposed to oxyhemoglobin and supernatant fluid appeared identical to cells contracted with PGF2 alpha. The outer surface of cells of arteries exposed to bilirubin, methemoglobin, and mock cerebrospinal fluid were normal. Marked similarity between vasospastic smooth muscle cells and smooth muscle cells from arteries contracted with PGF2 alpha suggest that smooth muscle contraction occurs during "vasospasm" due to whole blood and to intrathecal injection of oxyhemoglobin.

Animals↗
PubMed1989

Cytoplasmic Ca2+ is a primary determinant for myosin phosphorylation in smooth muscle cells.

Initiation of smooth muscle contraction is associated with Ca2+/calmodulin activation of myosin light chain kinase which catalyzes the phosphorylation of the 20-kDa light chain of myosin. In tracheal smooth muscle cells in culture, the extent of myosin light chain phosphorylation is less than 10% at basal cytosolic free Ca2+ concentrations of 150 nM. Stimulation of these cells with serotonin, histamine, carbachol, or the Ca2+ ionophore, ionomycin, increases free cytosolic Ca2+ concentrations and the extent of myosin light chain phosphorylation. Light chain phosphorylation reaches a maximal value of 67% at Ca2+ concentrations below 1 microM. The relationship between the extent of light chain phosphorylation and cytosolic free Ca2+ concentration is apparently independent of the source of free intracellular Ca2+ or the agent used to stimulate the cells and is not altered by pre-exposure of the contractile apparatus to high concentrations of free Ca2+. Pretreatment of cells with 8-bromo-cyclic GMP or forskolin decreases free cytosolic Ca2+ concentrations and the extent of myosin light chain phosphorylation in response to histamine or ionomycin. Pretreatment with 8-bromo-cyclic GMP also decreases the maximal extent of light chain phosphorylation. These results indicate that cytosolic free Ca2+ concentration, per se, is a primary determinant for myosin light chain phosphorylation in tracheal smooth muscle cells.

Animals↗
PubMed2000

Potassium channels in gastrointestinal smooth muscle.

1. Electromechanical coupling in smooth muscle serves to coordinate the contractile activity of the syncytium. Electrical activity of smooth muscle of the gut is generated by ionic conductances that regulate and in turn are regulated by the membrane potential of smooth muscle cells. This activity determines the extent of Ca2+ entry into smooth muscle cells, and thus, the timing and intensity of contractions. 2. Potassium channels play an important role in regulating the excitability of the syncytium. The different types of K+ channel are characterized by different sensitivities to membrane potential, to intracellular Ca2+ levels and to modulation by agonists. 3. This review highlights the different types of K+ channels found in gut smooth muscle and describes their possible roles in regulating the electrical activity of the muscle.

Animals↗
PubMed1997

cAMP induces heme oxygenase-1 gene expression and carbon monoxide production in vascular smooth muscle.

Recent studies indicate that vascular smooth muscle cells generate carbon monoxide (CO) via the action of heme oxygenase (HO). Because adenosine 3',5'-cyclic monophosphate (cAMP) is an important intracellular signaling molecule in the regulation of vascular cell function, we examined whether this second messenger modulates the expression of HO and the production of CO by rat aortic smooth muscle cells. Treatment of smooth muscle cells with the membrane-permeable cAMP derivative dibutyryl cAMP or with compounds that increase intracellular cAMP levels (isoproterenol and forskolin) resulted in a concentration- and time-dependent increase in the levels of HO-1 mRNA and protein, whereas the expression of HO-2 remained unchanged. Both actinomycin D and cycloheximide blocked the basal expression of HO-1 mRNA and protein and prevented the cAMP-mediated induction of HO-1. Incubation of platelets with cAMP-treated smooth muscle cells resulted in a significant increase in platelet cGMP concentration that was partially reversed by treatment of smooth muscle cells with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine or the HO blocker zinc protoporphyrin-IX. However, the combined addition of these two inhibitors to cAMP-treated smooth muscle cells or the addition of the CO and NO scavenger hemoglobin to platelets completely blocked the stimulatory effect on platelet cGMP levels. These results demonstrate that cAMP induces the expression of the HO-1 gene and stimulates the formation of CO and NO in vascular smooth muscle cells. The capacity of cAMP to induce the synthesis of guanylate cyclase-stimulatory CO from smooth muscle cells may represent a novel mechanism by which this nucleotide regulates vascular tone.

Animals↗