On the Action of General Anesthetics on Cellular Function: Barbiturate Alters the Exocytosis of Catecholamines in a Model Cell System

ChemPhysChem ◽  
2018 ◽  
Vol 19 (10) ◽  
pp. 1173-1179 ◽  
Author(s):  
Daixin Ye ◽  
Andrew Ewing
2013 ◽  
Vol 102 (3) ◽  
pp. 852-861 ◽  
Author(s):  
Paul A. Turner ◽  
C. Andrew Weeks ◽  
Austin J. McMurphy ◽  
Amol V. Janorkar

2011 ◽  
Vol 25 (8) ◽  
pp. 1416-1430 ◽  
Author(s):  
Geneva DeMars ◽  
Francesca Fanelli ◽  
David Puett

The mechanisms of G protein coupling to G protein-coupled receptors (GPCR) share general characteristics but may exhibit specific interactions unique for each GPCR/G protein partnership. The extreme C terminus (CT) of G protein α-subunits has been shown to be important for association with GPCR. Hypothesizing that the extreme CT of Gαs is an essential component of the molecular landscape of the GPCR, human LH receptor (LHR), and β2-adrenergic receptor (β2-AR), a model cell system was created for the expression and manipulation of Gαs subunits in LHR+ s49 ck cells that lack endogenous Gαs. On the basis of studies involving truncations, mutations, and chain extensions of Gαs, the CT was found to be necessary for LHR and β2-AR signaling. Some general similarities were found for the responses of the two receptors, but significant differences were also noted. Computational modeling was performed with a combination of comparative modeling, molecular dynamics simulations, and rigid body docking. The resulting models, focused on the Gαs CT, are supported by the experimental observations and are characterized by the interaction of the four extreme CT amino acid residues of Gαs with residues in LHR and β2-AR helix 3, (including R of the DRY motif), helix 6, and intracellular loop 2. This portion of Gαs recognizes the same regions of the two GPCR, although with differences in the details of selected interactions. The predicted longer cytosolic extensions of helices 5 and 6 of β2-AR are expected to contribute significantly to differences in Gαs recognition by the two receptors.


2013 ◽  
Vol 85 (4-5) ◽  
pp. 161-172 ◽  
Author(s):  
Simon Schulz ◽  
Thorsten Steinberg ◽  
David Beck ◽  
Pascal Tomakidi ◽  
Rosita Accardi ◽  
...  
Keyword(s):  
Hpv16 E6 ◽  

2005 ◽  
Vol 70 (5) ◽  
pp. 762-769 ◽  
Author(s):  
J.K. Richards ◽  
W. Abdel-Razaq ◽  
T.E. Bates ◽  
D.A. Kendall

2006 ◽  
Vol 34 (4) ◽  
pp. 468-471 ◽  
Author(s):  
D. Willoughby ◽  
D.M.F. Cooper

cAMP is a ubiquitous intracellular signalling molecule that can regulate a wide array of cellular processes. The diversity of action of this second messenger owes much to the localized generation, action and hydrolysis of cAMP within discrete subcellular regions. Further signalling specificity can be achieved by the ability of cells to modulate the frequency or incidence of such cAMP signals. Here, we discuss the use of two cAMP biosensors that measure real-time cAMP changes in the single cell, to address the mechanisms underlying the generation of dynamic cAMP signals. The first method monitors sub-plasmalemmal cAMP changes using mutant cyclic nucleotide-gated channels and identifies an AKAP (A-kinase-anchoring protein)–protein kinase A–PDE4 (phosphodiesterase-4) signalling complex that is central to the generation of dynamic cAMP transients in this region of the cell. The second study uses a fluorescence resonance energy transfer-based cAMP probe, based on Epac1 (exchange protein directly activated by cAMP 1), to examine interplay between Ca2+ and cAMP signals. This study demonstrates real-time oscillations in cAMP driven by a Ca2+-stimulated AC (adenylate cyclase) (AC8) and subsequent PDE4 activity. These studies, using two very different single-cell cAMP probes, broaden our understanding of the specific spatiotemporal characteristics of agonist-evoked cAMP signals in a model cell system.


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