scholarly journals Adenylyl cyclase isoforms and signal integration in models of vascular smooth muscle cells

2001 ◽  
Vol 281 (4) ◽  
pp. H1545-H1552 ◽  
Author(s):  
Jerry G. Webb ◽  
Phillip W. Yates ◽  
Qing Yang ◽  
Yurii V. Mukhin ◽  
Stephen M. Lanier
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Adenylyl Cyclase ◽  
Cell Line ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Ionophore A23187 ◽  
Signal Integration ◽  
A7r5 Cells

Adenylyl cyclases present a potential focal point for signal integration in vascular smooth muscle cells (VSMC) influencing contractile state and cellular responses to vessel wall injury. In the present study, we examined the influence of the vasoactive peptide arginine vasopressin (AVP) on cAMP regulation in primary cultures of rat aortic VSMC and in the A7r5 arterial smooth muscle cell line. In cultured VSMC and A7r5 cells, AVP had no effect on basal cAMP but differentially affected β-adrenergic receptor-induced activation of adenylyl cyclase. AVP synergistically increased (twofold) isoproterenol-stimulated cAMP production in VSMC but inhibited the effect of isoproterenol (50%) in the A7r5 cell line. The effects of AVP in both preparations were blocked when cells were pretreated with a selective V1vasopressin receptor antagonist. Moreover, the actions of AVP in both models were dependent on release of intracellular Ca2+ and were mimicked by elevation of Ca2+ with the ionophore A23187 , suggesting that the responses to AVP involve Ca2+-mediated regulation of adenylyl cyclase stimulation. Adenylyl cyclase types I, III, and VIII are stimulated by Ca2+/calmodulin, whereas types V and VI are directly inhibited by Ca2+. RNA blot analysis for effector isotypes indicated that both VSMC and A7r5 cells expressed types III, V, and VI. VSMC also expressed mRNA for type IV and VIII effectors, which could account for the cell-specific responses to peptide hormone and Ca2+.

Surface thrombomodulin modulates thrombin receptor responses on vascular smooth muscle cells

1996 ◽  
Vol 270 (2) ◽  
pp. H603-H609 ◽  
Author(s):  
B. W. Grinnell ◽  
D. T. Berg
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cell Line ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cellular Responses ◽  
Thrombin Receptor ◽  
Mitogenic Response ◽  
Agonist Peptide

Vascular smooth muscle cells produce the proteolytically activated thrombin receptor. Under certain conditions, they have been reported to synthesize thrombomodulin (TM), another thrombin receptor known to convert the specificity of thrombin from cleavage of procoagulant/proinflammatory substrates to the cleavage of the anticoagulant/anti-inflammatory factor protein C. In this study, we examined the role of TM in modulating thrombin-mediated cellular responses. Using a thrombin receptor-positive TM-negative rabbit intimal smooth muscle cell line (RIC), we isolated cells expressing varying levels of functional surface TM after transfection with an expression vector containing the cDNA for full-length TM. The parent RIC (TM negative) line responded to alpha-thrombin and to agonist peptide (SFLLRN-PNDKYEPF; abbreviated SFLL) with both mitogenic response and phosphoinositol release. However, transfected cells producing high levels of TM, equivalent to the level on rabbit aortic endothelial cells, responded to SFLL but not to alpha-thrombin. Whereas alpha-thrombin, SFLL, and the combination of SFLL and thrombin resulted in a mitogenic response in the TM-negative RIC line, the response to the agonist peptide could be blocked by thrombin in the TM-producing cell line. The degree to which thrombin receptor activation was blocked directly correlated with the level of TM on the cell surface, and high levels of thrombin could overcome the inhibitory effect. Our data demonstrate that the coexpression of TM with thrombin receptor on vascular smooth muscle cells can result in a modulation of cellular responses to thrombin, which could control thrombin-induced proliferative events following vessel injury or insult.

scholarly journals Principal role of adenylyl cyclase 6 in K+ channel regulation and vasodilator signalling in vascular smooth muscle cells

2011 ◽  
Vol 91 (4) ◽  
pp. 694-702 ◽  
Author(s):  
Carl P. Nelson ◽  
Richard D. Rainbow ◽  
Jennifer L. Brignell ◽  
Matthew D. Perry ◽  
Jonathon M. Willets ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Adenylyl Cyclase ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
K Channel ◽  
Principal Role ◽  
Channel Regulation

Adenylyl cyclase-cAMP system inhibits thrombin-induced HSP27 in vascular smooth muscle cells

2005 ◽  
Vol 94 (3) ◽  
pp. 573-584 ◽  
Author(s):  
Kouseki Hirade ◽  
Kumiko Tanabe ◽  
Masayuki Niwa ◽  
Akira Ishisaki ◽  
Keiichi Nakajima ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Adenylyl Cyclase ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Camp System

Adenylyl cyclase isoforms and vasopressin enhancement of agonist-stimulated cAMP in vascular smooth muscle cells

1997 ◽  
Vol 273 (2) ◽  
pp. H971-H980 ◽  
Author(s):  
J. Zhang ◽  
M. Sato ◽  
E. Duzic ◽  
S. W. Kubalak ◽  
S. M. Lanier ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Adenylyl Cyclase ◽  
Vascular Smooth Muscle Cells ◽  
Focal Point ◽  
Muscle Cells ◽  
Type Iii ◽  
Camp Formation ◽  
Camp Stimulation

The influence of arginine vasopressin (AVP) on agonist-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation was investigated in vascular smooth muscle cells (VSMC) cultured from rat thoracic aorta. Incubation of VSMC with AVP for 60 s produced a 2- to 2.5-fold enhancement of isoproterenol-induced cAMP formation. AVP also increased cAMP stimulation by the prostaglandin I2 analogue iloprost. The effect of AVP to enhance agonist-stimulated cAMP formation was completely inhibited in cells pretreated with a selective antagonist of V1 vasopressin receptors but was not affected by blockade of V2 receptors. Inhibition of protein kinase C activation failed to alter the action of AVP to potentiate cAMP stimulation, but treatment of cells with calmodulin antagonists significantly attenuated this effect of the peptide. Moreover, depletion of Ca2+ stores with thapsigargin decreased AVP enhancement of isoproterenol-stimulated cAMP by > 70%. The action of AVP to increase cAMP stimulation was also demonstrated in freshly isolated strips of rat aorta where treatment with peptide produced a twofold increase in isoproterenol-stimulated cAMP formation. RNA blot analysis indicated expression in VSMC of mRNA encoding type III adenylyl cyclase, a Ca(2+)-calmodulin-sensitive isoform of the effector. Furthermore, when detergent-solubilized membrane extract was subjected to calmodulin affinity chromatography, a peak of adenylyl cyclase activity was identified which had affinity for calmodulin matrix in the presence of Ca2+. The results indicate that AVP activates V1 receptors in VSMC to enhance agonist-stimulated cAMP formation by a Ca(2+)-calmodulin-dependent mechanism and suggest that type III adenylyl cyclase may provide a focal point in the VSMC for cross talk between constrictor and dilator pathways.

scholarly journals Novel transcripts of Nox1 are regulated by alternative promoters and expressed under phenotypic modulation of vascular smooth muscle cells

2006 ◽  
Vol 398 (2) ◽  
pp. 303-310 ◽  
Author(s):  
Noriaki Arakawa ◽  
Masato Katsuyama ◽  
Kuniharu Matsuno ◽  
Norifumi Urao ◽  
Yoshiaki Tabuchi ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Nadph Oxidase ◽  
Smooth Muscle Cells ◽  
Cell Line ◽  
Vascular Smooth Muscle Cells ◽  
Vascular Tissue ◽  
Muscle Cells ◽  
Alternative Promoters ◽  
Phenotypic Modulation

NADPH oxidase is implicated in the pathogenesis of various cardiovascular disorders. In vascular smooth muscle cells (VSMC), expression of NOX1 (NADPH oxidase 1), a catalytic subunit of NADPH oxidase, is low and is induced upon stimulation by vasoactive factors, while it is abundantly expressed in colon epithelial cells. To clarify the regulatory mechanisms underlying such cell-specific expression, the upstream regions directing transcription of the NOX1 gene were explored. In P53LMACO1 cells, a cell line originated from mouse VSMCs, two novel Nox1 mRNA species, the c- and f-type, were isolated. These transcripts contained 5′-untranslated regions that differed from the colon type mRNA (a-type) and encoded an additional N-terminal peptide of 28 amino acids. When these transcripts were fused to the c-myc tag and expressed in human embryonic kidney 293 cells, a fraction of translated proteins demonstrated the size containing the additional peptide. Proteins encoded by the c- and f-type mRNAs exhibited superoxide-producing activities equivalent to the activity of the a-type form. The a-type mRNA was expressed in the colon and in the intact aorta, whereas the c-type mRNA was detected in the primary cultured VSMCs migrated from aortic explants, in vascular tissue of a wire-injury model and in the thoracic aorta of mice infused with angiotensin II. The promoter region of the c-type mRNA exhibited transcriptional activity in P53LMACO1 cells, but not in MCE301 cells, a mouse colon epithelial cell line. These results suggest that expression of the Nox1 gene is regulated by alternative promoters and that the novel c-type transcript is induced under phenotypic modulation of VSMCs.

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