Regulation of glucose transport in aortic smooth muscle cells by cAMP and cGMP

2001 ◽  
Vol 353 (3) ◽  
pp. 513-519 ◽  
Author(s):  
Christopher J. MacKENZIE ◽  
Jill M. WAKEFIELD ◽  
Fiona CAIRNS ◽  
Anna F. DOMINICZAK ◽  
Gwyn W. GOULD
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Smooth Muscle Cells ◽  
Primary Cultures ◽  
Muscle Cells ◽  
Mek Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Common Element ◽  
Dependent Manner ◽  
Concentration Dependent Manner

We have studied the ability of cGMP and cAMP to modulate platelet-derived growth factor (PDGF)-stimulated 2-deoxy-d-glucose (deGlc) transport in primary cultures of vascular smooth muscle cells (VMSC) from rat aorta. PDGF stimulated deGlc transport in a time- and concentration-dependent manner. 8-Bromo-cGMP and atrial natriuretic peptide(1–28) [ANP(1–28)] were found to reduce PDGF-stimulated deGlc transport without affecting basal (unstimulated) transport activity. In contrast, 8-bromo-cAMP and dibutyryl-cAMP stimulated basal deGlc transport 2-fold and were without effect on PDGF-stimulated deGlc transport. 8-Bromo-cGMP also inhibited 8-bromo-cAMP-stimulated deGlc transport. The stimulation of deGlc transport by PDGF was sensitive to the mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK) kinase (MEK) inhibitor PD98059, and we show that ERK1/2 was activated by PDGF. Neither 8-bromo-cGMP nor ANP(1–28) inhibited PDGF-stimulated ERK activation, suggesting that the effects of cGMP and ANP(1–28) were not mediated by inhibition of this kinase. Our data also argue against a role for cGMP-dependent protein kinase in mediating the effects of cGMP or ANP(1–28). Collectively, our data suggest that in VSMC: (i) cGMP and cAMP have opposing effects on deGlc transport; (ii) PDGF and cAMP have common elements in the pathways by which they activate deGlc transport; and (iii) a common element may be the target of the cGMP-mediated inhibition of deGlc transport.

scholarly journals N-terminal pyroglutamate formation in CX3CL1 is essential for its full biologic activity

2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Astrid Kehlen ◽  
Monique Haegele ◽  
Livia Böhme ◽  
Holger Cynis ◽  
Torsten Hoffmann ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Smooth Muscle Cells ◽  
Adhesion Molecule ◽  
Muscle Cells ◽  
Mitogen Activated Protein Kinase ◽  
Intercellular Adhesion Molecule ◽  
Dependent Manner ◽  
Glutaminyl Cyclase ◽  
N Terminus

CX3CL1 (fractalkine) is a unique member of the CX3C chemokine family and mediates both adhesion and cell migration in inflammatory processes. Frequently, the activity of chemokines depends on a modified N-terminus as described for the N-terminus of CCL2 modified to a pGlu- (pyroglutamate) residue by QC (glutaminyl cyclase) activity. Here, we assess the role of the pGlu-modified residue of the CX3CL1 chemokine domain in human endothelial and smooth muscle cells. For the first time, we demonstrated using MS that QC (QPCT, gene name of QC) or its isoenzyme isoQC (iso-glutaminyl cyclase) (QPCTL, gene name of isoQC) catalyse the formation of N-terminal-modified pGlu-CX3CL1. Expression of QPCT is co-regulated with its substrates CCL2 and CX3CL1 in HUVECs (human umbilical vein endothelial cells) and HCASMCs (human coronary artery smooth muscle cells) upon stimulation with TNF-α and IL-1β whereas QPCTL expression is not affected. By contrast, inhibition of the NF-κB pathway using an IKK2 inhibitor decreased the expression of the co-regulated targets QPCT, CCL2, and CX3CL1. Furthermore, RNAi-mediated inhibition of QPCT expression resulted in a reduction in CCL2 and CX3CL1 mRNA. In HCASMCs, N-terminal-modified pGlu1-CX3CL1 induced a significant stronger effect on phosphorylation of ERK (extracellular signal regulated kinase) 1/2, Akt (protein kinase B), and p38 (p38 mitogen-activated protein kinase) kinases than the immature Gln1-CX3CL1 in a time- and concentration-dependent manner. Furthermore, pGlu1-CX3CL1 affected the expression of CCL2, CX3CL1, and the adhesion molecule ICAM1/CD54 (intercellular adhesion molecule-1) inducing in higher expression level compared with its Gln1-variant in both HCASMCs and HUVECs. These results strongly suggest that QC-catalysed N-terminal pGlu formation of CX3CL1 is important for the stability or the interaction with its receptor and opens new insights into the function of QC in inflammation.

Modulation of smooth muscle contraction by sphingosylphosphorylcholine

1995 ◽  
Vol 269 (3) ◽  
pp. G370-G377 ◽  
Author(s):  
K. N. Bitar ◽  
H. Yamada
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Smooth Muscle Cells ◽  
Map Kinase ◽  
Intracellular Signaling ◽  
Calcium Release ◽  
Muscle Cells ◽  
Smooth Muscle Contraction ◽  
Mitogen Activated Protein Kinase ◽  
Maximal Response

We have investigated the effect of sphingosylphosphorylcholine (SPC), a synthetic product that was implicated in the sphingomyelin cycle, and have assessed its role in intracellular signaling. SPC induced a dose-dependent contractile effect of smooth muscle cells isolated from the rectosigmoid of the rabbit. Maximal contraction occurred at 10(-6) M. The response started early, 25.4 +/- 6% shortening at 15 s, peaked at 30 s (32.5 +/- 2%), and remained sustained at 8 min (30.0 +/- 3.5%). Preincubation of the cells with thapsigargin had no effect on contraction induced by SPC. The response to a combination of threshold concentrations of inositol 1,4,5-trisphosphate (IP3) and SPC was additive and was significantly different from the maximal response elicited by each agent alone. SPC also induced activation of mitogen-activated protein kinase (MAP kinase). This study demonstrates that SPC is important in cellular signaling of gastrointestinal smooth muscle cells through a mechanism that is independent of IP3-sensitive calcium release and probably through activation of a protein kinase C-mediated activation of MAP kinase.

Differential blockade of agonist- and depolarization-induced 45Ca2+ influx in smooth muscle cells

1989 ◽  
Vol 257 (4) ◽  
pp. C607-C611 ◽  
Author(s):  
A. Wallnofer ◽  
C. Cauvin ◽  
T. W. Lategan ◽  
U. T. Ruegg
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle ◽  
Gamma S ◽  
Ca2 Channels ◽  
Stimulation Of

ATP stimulated 45Ca2+ influx in rat aortic smooth muscle cells in a concentration-dependent manner (EC50 = 3.6 +/- 0.5 X 10(-7) M). ADP and GTP were less effective than ATP in stimulating 45Ca2+ influx; AMP was weakly active and the adenosine agonist 5'-(N-ethyl-carboxamido)-adenosine (NECA) had no effect. ATP gamma S was about equieffective with ATP, whereas alpha,beta-methylene-ATP (APCPP) did not induce 45Ca2+ influx. Stimulation of 45Ca2+ influx by ATP was not abolished by the dihydropyridine Ca2+ channel antagonist darodipine (PY 108-068), which completely blocked depolarization-induced 45Ca2+ influx. Inorganic cations (La3+, Cd2+, Co2+, Ni2+, Mn2+, and Mg2+) were able to inhibit both agonist- and depolarization-induced 45Ca2+ influx. Cd2+, however, was approximately 20 times more selective in blocking K+-stimulated than agonist-stimulated 45Ca2+ influx. These data indicate that ATP-stimulated Ca2+ influx in rat aortic smooth muscle cells is resistant to darodipine but is reduced by La3+, Cd2+, and other inorganic blockers of Ca2+ channels.

Role of IL-4, IL-13, and STAT6 in inflammation-induced hypercontractility of murine smooth muscle cells

2002 ◽  
Vol 282 (2) ◽  
pp. G226-G232 ◽  
Author(s):  
Hirotada Akiho ◽  
Patricia Blennerhassett ◽  
Yikang Deng ◽  
Stephen M. Collins
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Trichinella Spiralis ◽  
Muscle Cells ◽  
Dependent Manner ◽  
T Helper ◽  
Concentration Dependent Manner ◽  
T Helper 2 ◽  
Muscularis Externa

T helper 2 (Th2) cytokines interleukin (IL)-4 and IL-13, which activate signal transducer and activator of transcription 6 (STAT6) are expressed in the muscularis externa during nematode infection and are candidate mediators of the associated hypercontractility. To determine the locus of action of these cytokines, we examined the IL-4- and IL-13-induced hypercontractility of the isolated muscle cells from STAT6 +/+ and STAT6 −/− mice. We compared the results with cells isolated from Trichinella spiralis-infected STAT6 +/+ and STAT6 −/− mice. Carbamylcholine chloride (Carbachol) induced the contraction of jejunal muscle cells in a concentration-dependent manner maximal contraction (Rmax26.7 ± 1.9%). Cells from T. spiralis-infected STAT6 −/− mice showed the hypertrophy (cell lengths 41.4 ± 0.8 to 89.0 ± 8.7 μm) and hypercontractility (Rmax37.5 ± 1.3%) induced by infection. IL-4Rα mRNA was detected in dispersed smooth muscle cells. Incubation of longitudinal muscle-myenteric plexus (LMMP) with IL-4 and IL-13 enhanced Carbachol-induced muscle contraction (Rmax35.5 ± 1.9 and 32.4 ± 2.9%, respectively). Incubation of LMMP from STAT6 −/− mice with IL-4 did not enhance the contraction. The hypercontractility in T. spiralis-infected mice was attenuated in STAT6 −/− mice ( P < 0.02). These results indicate both IL-4 and IL-13 induce hypercontractility of muscle cells via the STAT6 pathway, and this is the basis for hypercontractility observed in T. spiralis-infected mice.

scholarly journals The contribution of inositol 1,4,5-trisphosphate and ryanodine receptors to agonist-induced Ca2+ signaling of airway smooth muscle cells

2009 ◽  
Vol 297 (2) ◽  
pp. L347-L361 ◽  
Author(s):  
Yan Bai ◽  
Martin Edelmann ◽  
Michael J. Sanderson
Keyword(s):  
Wave Propagation ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Ryanodine Receptors ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Inositol 1,4,5 Trisphosphate

The relative contribution of inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) and ryanodine receptors (RyRs) to agonist-induced Ca2+ signaling in mouse airway smooth muscle cells (SMCs) was investigated in lung slices with phase-contrast or laser scanning microscopy. At room temperature (RT), methacholine (MCh) or 5-hydroxytryptamine (5-HT) induced Ca2+ oscillations and an associated contraction in small airway SMCs. The subsequent exposure to an IP3R antagonist, 2-aminoethoxydiphenyl borate (2-APB), inhibited the Ca2+ oscillations and induced airway relaxation in a concentration-dependent manner. 2-APB also inhibited Ca2+ waves generated by the photolytic release of IP3. However, the RyR antagonist ryanodine had no significant effect, at any concentration, on airway contraction or agonist- or IP3-induced Ca2+ oscillations or Ca2+ wave propagation. By contrast, a second RyR antagonist, tetracaine, relaxed agonist-contracted airways and inhibited agonist-induced Ca2+ oscillations in a concentration-dependent manner. However, tetracaine did not affect IP3-induced Ca2+ release or wave propagation nor the Ca2+ content of SMC Ca2+ stores as evaluated by Ca2+-release induced by caffeine. Conversely, both ryanodine and tetracaine completely blocked agonist-independent slow Ca2+ oscillations induced by KCl. The inhibitory effects of 2-APB and absence of an effect of ryanodine on MCh-induced airway contraction or Ca2+ oscillations of SMCs were also observed at 37°C. In Ca2+-permeable SMCs, tetracaine inhibited agonist-induced contraction without affecting intracellular Ca2+ levels indicating that relaxation also resulted from a reduction in Ca2+ sensitivity. These results indicate that agonist-induced Ca2+ oscillations in mouse small airway SMCs are primary mediated via IP3Rs and that tetracaine induces relaxation by both decreasing Ca2+ sensitivity and inhibiting agonist-induced Ca2+ oscillations via an IP3-dependent mechanism.

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