Cardiovascular α1-adrenoceptor subtypes: functions and signaling

2000 ◽  
Vol 78 (4) ◽  
pp. 267-292 ◽  
Author(s):  
Daya R Varma ◽  
Xing-Fei Deng
Keyword(s):  
Cardiac Hypertrophy ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Mitogen Activated Protein Kinase ◽  
Major Function ◽  
Cardiac Inotropy ◽  
Mitogen Activated Protein ◽  
Intracellular Ca ◽  
Inotropic Responses ◽  
G Protein Coupled

α1-Adrenoceptors (α1AR) are G protein-coupled receptors and include α1A, α1B, and α1D subtypes corresponding to cloned α1a, α1b, and α1d, respectively. α1AR mediate several cardiovascular actions of sympathomimetic amines such as vasoconstriction and cardiac inotropy, hypertrophy, metabolism, and remodeling. α1AR subtypes are products of separate genes and differ in structure, G protein-coupling, tissue distribution, signaling, regulation, and functions. Both α1AAR and α1BAR mediate positive inotropic responses. On the other hand, cardiac hypertrophy is primarily mediated by α1AAR. The only demonstrated major function of α1DAR is vasoconstriction. α1AR are coupled to phospholipase C, phospholipase D, and phospholipase A2; they increase intracellular Ca2+ and myofibrillar sensitivity to Ca2+ and cause translocation of specific phosphokinase C isoforms to the particulate fraction. Cardiac hypertrophic responses to α1AR agonists might involve activation of phosphokinase C and mitogen-activated protein kinase via Gq. α1AR subtypes might interact with each other and with other receptors and signaling mechanisms.Key words: cardiac hypertrophy, inotropic responses, central α1-adrenoreceptors, arrythmias.

Role of endocytosis in signalling and regulation of G-protein-coupled receptors

2001 ◽  
Vol 29 (4) ◽  
pp. 500-504 ◽  
Author(s):  
M. von Zastrow
Keyword(s):  
G Protein ◽  
Adrenergic Receptors ◽  
G Protein Coupled Receptors ◽  
Mitogen Activated Protein Kinase ◽  
Vesicular Carriers ◽  
Mitogen Activated Protein ◽  
Effector Pathways ◽  
Endocytic Vesicles ◽  
G Protein Coupled

Many G-protein-coupled receptors (GPCRs) undergo agonist-induced endocytosis. Endocytosis contributes to distinct processes that regulate the number and functional activity of receptors present in the plasma membrane, contributing to the well described processes of receptor sequestration and down-regulation. Emerging evidence suggests additional functions of endocytosis in mediating GPCR signalling via certain effector pathways, such as mitogen-activated protein kinase modules. The diverse functions of endocytosis raise fundamental questions about the nature of the vesicular carriers and membrane pathways that mediate the endocytic trafficking of specific GPCRs. Insights into the biochemical and functional properties of endocytic vesicles containing internalized opioid and adrenergic receptors will be discussed. Progress towards understanding the mechanisms that control the specificity with which distinct GPCRs are sorted to specialized sub-populations of endocytic vesicles will be highlighted.

scholarly journals Ras-dependent Mitogen-activated Protein Kinase Activation by G Protein-coupled Receptors

1997 ◽  
Vol 272 (31) ◽  
pp. 19125-19132 ◽  
Author(s):  
Gregory J. Della Rocca ◽  
Tim van Biesen ◽  
Yehia Daaka ◽  
Deirdre K. Luttrell ◽  
Louis M. Luttrell ◽  
...  
Keyword(s):  
Protein Kinase ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Mitogen Activated Protein Kinase ◽  
Kinase Activation ◽  
Protein Kinase Activation ◽  
Mitogen Activated Protein ◽  
G Protein Coupled

scholarly journals Pleiotropic Coupling of G Protein-coupled Receptors to the Mitogen-activated Protein Kinase Cascade

1999 ◽  
Vol 274 (20) ◽  
pp. 13978-13984 ◽  
Author(s):  
Gregory J. Della Rocca ◽  
Stuart Maudsley ◽  
Yehia Daaka ◽  
Robert J. Lefkowitz ◽  
Louis M. Luttrell
Keyword(s):  
Protein Kinase ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Kinase Cascade ◽  
G Protein Coupled ◽  
Protein Kinase Cascade

G-protein-coupled-receptor activation of the smooth muscle calponin gene

2001 ◽  
Vol 357 (2) ◽  
pp. 587-592 ◽  
Author(s):  
Nickolai O. DULIN ◽  
Sergei N. ORLOV ◽  
Chad M. KITCHEN ◽  
Tatyana A. VOYNO-YASENETSKAYA ◽  
Joseph M. MIANO
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
G Protein ◽  
Transcriptional Activation ◽  
Fold Increase ◽  
Receptor Activation ◽  
G Protein Coupled Receptors ◽  
Mitogen Activated Protein Kinase ◽  
G Protein Coupled

A hallmark of cultured smooth muscle cells (SMCs) is the rapid down-regulation of several lineage-restricted genes that define their in vivo differentiated phenotype. Identifying factors that maintain an SMC differentiated phenotype has important implications in understanding the molecular underpinnings governing SMC differentiation and their subversion to an altered phenotype in various disease settings. Here, we show that several G-protein coupled receptors [α-thrombin, lysophosphatidic acid and angiotensin II (AII)] increase the expression of smooth muscle calponin (SM-Calp) in rat and human SMC. The increase in SM-Calp protein appears to be selective for G-protein-coupled receptors as epidermal growth factor was without effect. Studies using AII showed a 30-fold increase in SM-Calp protein, which was dose- and time-dependent and mediated by the angiotensin receptor-1 (AT1 receptor). The increase in SM-Calp protein with AII was attributable to transcriptional activation of SM-Calp based on increases in steady-state SM-Calp mRNA, increases in SM-Calp promoter activity and complete abrogation of protein induction with actinomycin D. To examine the potential role of extracellular signal-regulated kinase (Erk1/2), protein kinase B, p38 mitogen-activated protein kinase and protein kinase C in AII-induced SM-Calp, inhibitors to each of the signalling pathways were used. None of these signalling molecules appears to be crucial for AII-induced SM-Calp expression, although Erk1/2 may be partially involved. These results identify SM-Calp as a target of AII-mediated signalling, and suggest that the SMC response to AII may incorporate a novel activity of SM-Calp.

scholarly journals Sphingosine 1-phosphate signalling through the G-protein-coupled receptor Edg-1

1998 ◽  
Vol 330 (2) ◽  
pp. 605-609 ◽  
Author(s):  
C. M. Gerben ZONDAG ◽  
R. Friso POSTMA ◽  
Ingrid VAN ETTEN ◽  
Ingrid VERLAAN ◽  
H. Wouter MOOLENAAR
Keyword(s):  
Adenylate Cyclase ◽  
Map Kinase ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Lpa Receptor ◽  
Kinase Activation ◽  
Protein Map ◽  
Mitogen Activated Protein ◽  
Sphingosine 1 Phosphate ◽  
G Protein Coupled

Sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) are structurally related lipid mediators that act on distinct G-protein-coupled receptors to evoke similar responses, including Ca2+ mobilization, adenylate cyclase inhibition, and mitogen-activated protein (MAP) kinase activation. However, little is still known about the respective receptors. A recently cloned putative LPA receptor (Vzg-1/Edg-2) is similar to an orphan Gi-coupled receptor termed Edg-1. Here we show that expression of Edg-1 in Sf9 and COS-7 cells results in inhibition of adenylate cyclase and activation of MAP kinase (Gi-mediated), but not Ca2+ mobilization, in response to S1P. These responses are specific in that (i) S1P action is not mimicked by LPA, and (ii) Vzg-1/Edg-2 cannot substitute for Edg-1. Thus the Edg-1 receptor is capable of mediating a subset of the cellular responses to S1P.

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