Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Muscle, Smooth”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources
PubMed1977

The effect of insulin and glucose on sterol synthesis in cultured rat arterial smooth muscle cells.

The smooth muscle cell plays an important role in the process of atherogenesis, proliferating in the arterial intima and becoming filled with lipid during the course of the disease. In these experiments the effect of insulin and glucose on sterol synthesis in cultured rat arterial smooth muscle cells was studied. Arterial smooth muscle cells were cultured from pieces of intima and inner media of young rat aortas. The cells were grown in Petri dishes in culture medium with foetal calf serum and when confluent were exposed to insulin or glucose for 24 hours. Insulin in concentrations of 10 micromicron-100 millimicron per ml stimulated the incorporation of sodium [2-(14)C]acetate into non-saponifiable lipids and digitonin precipitable sterols. However, insulin had no effect on the incorporation of labelled mevalonate into cell sterols. Increasing concentrations of glucose in the medium up to 140 mM had had no effect on the incorporation of isotope into sterols, but higher concentrations of glucose caused cell damage and sterol synthesis was markedly depressed. These results may have relevance to the development of atherosclerosis in diabetes and obesity.

Acetates↗
PubMed1990

Properties of calcium channels in cardiac muscle and vascular smooth muscle.

The voltage-dependent slow channels in the myocardial cell membrane are the major pathway by which Ca2+ ions enter the cell during excitation for initiation and regulation of the force of contraction of cardiac muscle. The slow channels have some special properties, including functional dependence on metabolic energy, selective blockade by acidosis, and regulation by the intracellular cyclic nucleotide levels. Because of these special properties of the slow channels, Ca2+ influx into the myocardial cell can be controlled by extrinsic factors (such as autonomic nerve stimulation or circulating hormones) and by intrinsic factors (such as cellular pH or ATP level). The slow Ca2+ channels of the heart are regulated by cAMP in a stimulatory fashion. Elevation of cAMP produces a very rapid increase in number of slow channels available for voltage activation during excitation. The probability of a slow channel opening and the mean open time of the channel are increased. Therefore, any agent that increases the cAMP level of the myocardial cell will tend to potentiate ISi, Ca2+ influx, and contraction. The myocardial slow Ca2+ channels are also regulated by cGMP, in a manner that is opposite to that of cAMP. The effect of cGMP is presumably mediated by means of phosphorylation of a protein, as for example, a regulatory protein (inhibitory-type) associated with the slow channel. Preliminary data suggest that calmodulin also may play a role in regulation of the myocardial slow Ca2+ channels, possibly mediated by the Ca2(+)-calmodulin-protein kinase and phosphorylation of some regulatory-type of protein. Thus, it appears that the slow Ca2+ channel is a complex structure, including perhaps several associated regulatory proteins, which can be regulated by a number of extrinsic and intrinsic factors. VSM cells contain two types of Ca2+ channels: slow (L-type) Ca2+ channels and fast (T-type) Ca2+ channels. Although regulation of voltage-dependent Ca2+ slow channels of VSM cells have not been fully clarified yet, we have made some progress towards answering this question. Slow (L-type, high-threshold) Ca2+ channels may be modified by phosphorylation of the channel protein or an associated regulatory protein. In contrast to cardiac muscle where cAMP and cGMP have antagonistic effects on Ca2+ slow channel activity, in VSM, cAMP and cGMP have similar effects, namely inhibition of the Ca2+ slow channels.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2006

Calcium sparklets regulate local and global calcium in murine arterial smooth muscle.

In arterial smooth muscle, protein kinase Calpha (PKCalpha) coerces discrete clusters of L-type Ca2+ channels to operate in a high open probability mode, resulting in subcellular domains of nearly continual Ca2+ influx called 'persistent Ca2+ sparklets'. Our previous work suggested that steady-state Ca2+ entry into arterial myocytes, and thus global [Ca2+]i, is regulated by Ca2+ influx through clusters of L-type Ca2+ channels operating in this persistently active mode in addition to openings of solitary channels functioning in a low-activity mode. Here, we provide the first direct evidence supporting this 'Ca2+ sparklet' model of Ca2+ influx at a physiological membrane potential and external Ca2+ concentration. In support of this model, we found that persistent Ca2+ sparklets produced local and global elevations in [Ca2+]i. Membrane depolarization increased Ca2+ influx via low-activity and high-activity persistent Ca2+ sparklets. Our data indicate that Ca2+ entering arterial smooth muscle through persistent Ca2+ sparklets accounts for approximately 50% of the total dihydropyridine-sensitive (i.e. L-type Ca2+ channel) Ca2+ influx at a physiologically relevant membrane potential (-40 mV) and external Ca2+ concentration (2 mm). Consistent with this, inhibition of basal PKCalpha-dependent persistent Ca2+ sparklets decreased [Ca2+]i by about 50% in isolated arterial myocytes and intact pressurized arteries. Taken together, these data support the conclusion that in arterial smooth muscle steady-state Ca2+ entry and global [Ca2+]i are regulated by low-activity and PKCalpha-dependent high-activity persistent Ca(2+) sparklets.

Animals↗
PubMed1988

Muscarinic receptor binding and Ca2+ influx in the all-or-none response to acetylcholine of isolated smooth muscle cells.

Isolated smooth muscle cells from guinea pig taenia caecum were prepared by collagenase digestion. Isolated single smooth muscle cells showed an all-or-none response to acetylcholine (ACh) under our experimental conditions. A Scatchard plot of the specific binding of [3H]quinuclidinyl benzilate (QNB) to the cells gave a straight line, and the KD and Bmax values were calculated as 0.18 +/- 0.03 nM and 1.11 +/- 0.10 pmol/mg protein, respectively. ACh competitively inhibited the specific binding of [3H]QNB in a concentration-dependent manner. Thus, although the cells showed an all-or-none response, ACh bound to the receptor concentration dependently. The contraction of the cells in response to ACh was inhibited in a concentration-dependent manner, by nicardipine suggesting that the contraction of smooth muscle cells in response to ACh depended on the influx of extracellular Ca2+. The ACh-stimulated increase of the Ca2+ influx was very rapid and correlated well with the contraction of the cells; it decreased after reaching a maximum. The all-or-none response of the cells could be due to a rapid influx of Ca2+. These results suggest that ACh binds to its receptor in a concentration-dependent manner, and that when the binding reaches a certain threshold, a rapid influx of Ca2+ occurs and the cells show an all-or-none response, followed by an efflux of Ca2+.

Acetylcholine↗
PubMed1992

Histidine-rich calcium binding protein, a sarcoplasmic reticulum protein of striated muscle, is also abundant in arteriolar smooth muscle cells.

Histidine-rich calcium binding protein (HRC) is a luminal sarcoplasmic reticulum protein abundant in skeletal and cardiac muscle. Using immunofluorescence to examine non-muscle tissues, we now show that HRC is also abundant in the smooth muscle cells lining the walls of small arteries and arterioles. Arterioles that contain only one or two layers of smooth muscle cells are very brightly stained while small muscular arteries demonstrate a lesser degree of immunoreactivity only in cells just adjacent to the lumen of the vessel. In contrast, visceral smooth muscle cells from the gastrointestinal and genitourinary tracts show no HRC immunofluorescence. We also examined the subcellular distribution of HRC in arteriolar smooth muscle by immunoelectron microscopy. HRC was found in electron-dense vesicles beneath the plasma membrane, in small electron-lucent vesicles and in the nuclear envelope, suggesting a location within a calcium-sequestering compartment. These findings suggest that HRC plays a role in sarcoplasmic reticulum function that is unique to striated and arteriolar smooth muscle.

Animals↗
PubMed1996

PDGF receptor-to-nucleus signaling of p91 (STAT1 alpha) transcription factor in rat smooth muscle cells.

Vascular smooth muscle cells (VSMC) are the predominant cell type in the media of a normal artery. Injury to the vessel wall leads to platelet deposition and the release of numerous factors, including PDGF, which exerts its biological effects by binding to specific surface receptors on the smooth muscle cell membrane. We demonstrate that PDGF-stimulated smooth muscle cells activate the STAT (signal transducers and activators of transcription) family of proteins in addition to other signaling pathways (e.g., RAS-RAF-MAP Kinase). We show that the transcription factor p91 (STAT1 alpha) is rapidly activated by PDGF in VSMC and specifically binds to the regulatory elements SIE or GAS. We hypothesize that signal transduction by p91 plays an important role in VSMC, especially after injury with the release of growth factors such as PDGF.

Animals↗
PubMed1995

T cell--vascular smooth muscle cell interactions: antigen-specific activation and cell cycle blockade of T helper clones by cloned vascular smooth muscle cells.

Histological observations have demonstrated the presence of T lymphocytes in atherosclerotic plaques, often in close association with vascular smooth muscle cells (VSMC). We have examined the interaction occurring between cloned murine VSMC and histocompatibility-matched, antigen-specific Th1 and Th2 cell lines. Incubation of either Th1 or Th2 cells with antigen-pulsed VSMC resulted in the formation of T cell-VSMC conjugates accompanied by morphological changes in both cell types. This interaction resulted in an antigen-dependent activation of IL-2 receptor expression by the Th cells, demonstrating the ability of cloned VSMC to process and present antigen through the exogenous pathway. However, although the T cells were activated to express IL-2 receptors by antigen-pulsed VSMC, they were unable to progress through cell cycle. The secretion of an inhibitory mediator by VSMC was suggested by the observations that (1) fixation of the VSMC's eliminated the inhibitory signal and (2) the supernatants of IFN gamma-primed VSMC displayed similar inhibitory activity. The inhibitory effect could not be abrogated with indomethacin or an inhibitor of the generation of reactive nitrogen intermediates, indicating that prostaglandin synthesis and/or nitric oxide production are not solely responsible for the inhibition of proliferation. Flow cytometric cell cycle analysis revealed that VSMC delivered signals resulting in a late G1 blockade of T cell cycle progression. Mitogen responses of purified primary T cells are also dramatically inhibited by IFN gamma-treated VSMC, despite significant IL-2 production. Our data depict a complex and intimate T cell-VSMC interaction and suggest that mutual activation events may occur.

Animals↗
PubMed1986

Induction of polyploidy in cultures of neonatal rat aortic smooth muscle cells.

Arterial smooth muscle cells become tetraploid with age and hypertension. To further study this phenomenon, neonatal rat aortic smooth muscle cells were placed in cell culture and studied over time. Numerous cells with tetraploid and even octaploid DNA content appeared beginning in primary cultures. These increases in DNA content per cell were determined by quantitative fluorescence microscopy and flow cytometry, and true polyploidy was confirmed by chromosome counts. In contrast, cells from adult rat aortas failed to produce significant polyploid cells over time in culture. In vitro culture of neonatal aortic cells may therefore be a model system for studying the initiation of polyploidy in arterial smooth muscle.

Actins↗
PubMed1997

Chronic carbachol pretreatment decreases adenylyl cyclase activity in airway smooth muscle.

In airway smooth muscle, the regulation of adenylyl cyclase, the enzyme that synthesizes adenosine 3',5'-cyclic monophosphate, is under dual regulation by G protein-coupled receptors. It is unknown if chronic activation of muscarinic receptors in airway smooth muscle alters the stimulatory adenylyl cyclase cascade to decrease airway relaxation. Bovine airway smooth muscle pretreated with carbachol for 18 h, but not for 30 min or 2 h, showed decreased adenylyl cyclase activity under basal conditions and in response to isoproterenol, prostaglandin E1, GTP, and forskolin. The quantity of beta-adrenergic receptors or of Gi alpha proteins was unaffected by carbachol pretreatment. The effect of carbachol pretreatment was blocked by the inclusion of atropine or the protein kinase C (PKC) inhibitor staurosporine. These results suggest that chronic but not acute agonist pretreatment of muscarinic receptors decreases in adenylyl cyclase stimulation at a site distal to receptors and that this effect is mediated by the chronic activation of PKC via the M3 muscarinic receptor.

Adenylyl Cyclases↗
PubMed1992

Airway epithelial cells regulate membrane potential, neurotransmission and muscle tone of the dog airway smooth muscle.

1. The effects of epithelial cells were investigated on resting membrane potential and neuro-effector transmission in smooth muscle cells of the dog tracheal and bronchiolar tissues. 2. The mean value of the resting membrane potential of the epithelium-intact bronchiolar smooth muscle cells of the dog was--70.0 +/- 1.1 mV (+/- S.D., n = 40) and mechanical denudation of the epithelial layer depolarized the membrane to -57.0 +/- 2.5 mV (+/- S.D., n = 40). Application of isolated and dispersed epithelial cells (greater than 2 x 10(5) cells/ml) to the perfusing solution repolarized the membrane of epithelium-denuded bronchiolar smooth muscle cells to -67.0 +/- 2.7 mV (+/- S.D., n = 20). The mean resting membrane potential of the mucosa-free tracheal smooth muscle cells was -59.1 +/- 1.4 mV (+/- S.D., n = 50), and application of isolated and dispersed cells (greater than 2 x 10(5) cells/ml) hyperpolarized the membrane to -67.2 +/- 1.8 mV (+/- S.D., n = 50). These repolarizing actions were not modified by indomethacin (10(-5) M). 3. In the epithelium-denuded bronchioles, ACh (greater than 10(-9) M) dose-dependently depolarized the smooth muscle cells, while in the epithelium-intact bronchioles, ACh (10(-11) - 10(-8) M) did not affect the resting membrane potential. At a concentration of 10(-7) M, ACh significantly depolarized the membrane. 4. Electrical field stimulation (EFS; 50 microseconds in duration and about 10-20 V in strength) applied to ring preparations of the bronchioles evoked twitch-like contractions (hereafter referred as twitch contraction), and size of the twitch contractions gradually and continuously decreased in the presence or absence of indomethacin (10(-5) M) and guanethidine (10(-6) M). When similar experiments were performed using epithelium-denuded bronchiolar ring preparations, in no case was there a prominent reduction in the amplitude of the twitch contractions in the presence of indomethacin and guanethidine. 5. The decremental response of the twitch contraction observed in the epithelium-intact bronchioles was overcome by application of the leukotriene synthesis inhibitor AA861 (10(-6) M) and the leukotriene antagonist ONO1078 (10(-5) M). 6. Leukotrienes C4 and D4 (LTC4 and LTD4, greater than 10(-8) M) evoked muscle contraction with a steady increase in muscle tone, up to a certain level. However, at 10(-9) M, LTC4 increased and LTD4 decreased the amplitude of the twitch contractions evoked by EFS in the epithelium-intact bronchioles.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Airway smooth muscle receptors.

Airway smooth muscle tone is influenced by many neurotransmitters, inflammatory mediators and drugs which interact direct or indirectly with specific surface receptors on smooth muscle cells. There have recently been important advances in our understanding of receptor mechanisms which may be relevant to understanding altered receptor function in airway inflammatory diseases. Neural control of airway tone is complex and several transmitters may be involved, including adrenoceptors, muscarinic receptors and receptors for various neuropeptides. Several inflammatory mediators, acting via specific receptors, may also influence airway smooth muscle. In the future molecular techniques which give information about the factors influencing receptor synthesis and post-translation processing will also provide further insights into understanding receptor function in airway disease.

Bronchi↗
PubMed2006

A novel mechanism of transcriptional repression of p27kip1 through Notch/HRT2 signaling in vascular smooth muscle cells.

Vascular smooth muscle cell (VSMC) proliferation occurs in vascular obstructive events such as atherosclerosis and restenosis. We previously showed that Notch receptors are induced in smooth muscle cells during vascular remodeling. Our goal was to determine the mechanisms employed by Notch signaling to regulate proliferation. Activation of Notch1 and Notch4 induced the VSMC-selective target genes HRT1 and HRT2, promoted cell cycle transit in smooth muscle cells, and led to loss of density-dependent growth inhibition. This was associated with a reduction in levels of the cyclin-dependent kinase inhibitor (cdk) p27(kip1). Over-expression of p27(kip1) resulted in a dose-dependent rescue of the Notch-induced phenotype and exit from the cell cycle. In addition, HRT2 expression was sufficient to promote S-phase entry, and we demonstrate that HRT2 interacts directly with the p27(kip1) promoter to repress transcription. Transcriptional repression occurred within the approximately 774 bp minimal p27(kip1) promoter region and mutational analysis demonstrated that repression is largely dependent on a conserved class-C domain. Our data show that Notch signaling acts to promote a proliferative phenotype in VSMC by modulation of the G1/S-phase checkpoint. In addition, we define a novel mechanism by which the Notch effector, HRT2, interacts directly with the class-C domain of the p27(kip1) promoter, repressing its expression. These studies identify a novel transcriptional target of HRT2, and show that Notch effectors directly control cell cycle regulatory components. We suggest that this mechanism is relevant to hyperproliferative states in VSMC seen during vascular remodeling and repair.

Adenoviridae↗