ARC Channels: A Novel Pathway for Receptor-Activated Calcium Entry

Physiology ◽  
2004 ◽  
Vol 19 (6) ◽  
pp. 355-361 ◽  
Author(s):  
Trevor J. Shuttleworth ◽  
Jill L. Thompson ◽  
Olivier Mignen
Keyword(s):  
Arachidonic Acid ◽  
Calcium Entry ◽  
Reciprocal Regulation ◽  
Functional Implications

In many nonexcitable cells, stimulation with low agonist concentrations specifically activates Ca2+ entry via arachidonic acid-regulated, highly Ca2+-selective ARC channels. Only at high agonist concentrations are the more widely studied store-operated channels activated, producing sustained elevated cytosolic Ca2+ concentration signals. These signals activate calcineurin, which in turn inhibits the ARC channels, resulting in a “reciprocal regulation” of these two distinct Ca2+-entry pathways that may have important functional implications for the cell.

Calcium entry and the control of calcium oscillations

2003 ◽  
Vol 31 (5) ◽  
pp. 916-919 ◽  
Author(s):  
T.J. Shuttleworth ◽  
O. Mignen
Keyword(s):  
Arachidonic Acid ◽  
Critical Role ◽  
Cell Types ◽  
Calcium Entry ◽  
Calcium Oscillations ◽  
Reciprocal Regulation ◽  
Crac Channels ◽  
Store Depletion ◽  
Low Concentrations ◽  
Ca2 Channels

During oscillatory Ca2+ signals, the agonist-induced enhanced entry of extracellular Ca2+ plays a critical role in modulating the frequency of the oscillations. Although it was originally assumed that the entry of Ca2+ under these conditions occurred via the well-known, and apparently ubiquitous, store-operated mechanism, subsequent studies suggested that this was unlikely. It is now known that, in many cell types, a novel non-capacitative Ca2+-selective pathway whose activation is dependent on arachidonic acid is responsible, and the channels involved [ARC channels (arachidonate-regulated Ca2+ channels)] have been characterized. These ARC channels co-exist with the store-operated CRAC channels (Ca2+-release-activated Ca2+ channel) in cells, but each plays a unique and non-overlapping role in Ca2+ signalling. In particular, it is the ARC channels that are specifically activated at the low agonist concentrations that give rise to oscillatory Ca2+ signals and provide the predominant mode of Ca2+ entry under these conditions. The indications are that Ca2+ entry through the ARC channels increases the likelihood that low concentrations of Ins(1,4,5)P3 will trigger repetitive Ca2+ release. At higher agonist concentrations, store-depletion is more complete and sustained resulting in the activation of CRAC channels. At the same time the ARC channels are turned off, resulting in what we have described as a reciprocal regulation of these two distinct Ca2+ entry pathways.

scholarly journals Reciprocal regulation of the nitric oxide and cyclooxygenase pathway in pathophysiology: relevance and clinical implications

2013 ◽  
Vol 304 (7) ◽  
pp. R473-R487 ◽  
Author(s):  
Daniela Salvemini ◽  
Sangwon F. Kim ◽  
Vincenzo Mollace
Keyword(s):  
Nitric Oxide ◽  
Arachidonic Acid ◽  
State Of The Art ◽  
No Synthase ◽  
In Vivo Studies ◽  
Clinical Implications ◽  
Reciprocal Regulation ◽  
Receptor Targets

The nitric oxide (NO) and cyclooxygenase (COX) pathways share a number of similarities. Nitric oxide is the mediator generated from the NO synthase (NOS) pathway, and COX converts arachidonic acid to prostaglandins, prostacyclin, and thromboxane A2. Two major forms of NOS and COX have been identified to date. The constitutive isoforms critically regulate several physiological states. The inducible isoforms are overexpressed during inflammation in a variety of cells, producing large amounts of NO and prostaglandins, which may underlie pathological processes. The cross-talk between the COX and NOS pathways was initially reported by Salvemini and colleagues in 1993, when they demonstrated in a series of in vitro and in vivo studies that NO activates the COX enzymes to produce increased amounts of prostaglandins. Those studies led to the concept that COX enzymes represent important endogenous “receptor” targets for amplifying or modulating the multifaceted roles of NO in physiology and pathology. Since then, numerous studies have furthered our mechanistic understanding of these interactions in pathophysiological settings and delineated potential clinical outcomes. In addition, emerging evidence suggests that the canonical nitroxidative species (NO, superoxide, and/or peroxynitrite) modulate biosynthesis of prostaglandins through non-COX-related pathways. This article provides a comprehensive state-of-the art overview in this area.

scholarly journals Mutual Antagonism of Calcium Entry by Capacitative and Arachidonic Acid-mediated Calcium Entry Pathways

2001 ◽  
Vol 276 (23) ◽  
pp. 20186-20189 ◽  
Author(s):  
Dali Luo ◽  
Lisa M. Broad ◽  
Gary St. J. Bird ◽  
James W. Putney
Keyword(s):  
Arachidonic Acid ◽  
Calcium Entry ◽  
Mutual Antagonism

Regulation of noncapacitative calcium entry by arachidonic acid and nitric oxide in endothelial cells

2005 ◽  
Vol 19 (14) ◽  
pp. 2075-2077 ◽  
Author(s):  
Annalisa Mottola ◽  
Susanna Antoniotti ◽  
Davide Lovisolo ◽  
Luca Munaron
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Arachidonic Acid ◽  
Calcium Entry

scholarly journals Nitric oxide co-ordinates the activities of the capacitative and non-capacitative Ca2+-entry pathways regulated by vasopressin

2003 ◽  
Vol 370 (2) ◽  
pp. 439-448 ◽  
Author(s):  
Zahid MONEER ◽  
Jeanette L. DYER ◽  
Colin W. TAYLOR
Keyword(s):  
Arachidonic Acid ◽  
Protein Kinase ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Protein Kinase G ◽  
Acid Activation ◽  
Reciprocal Regulation ◽  
A7r5 Cells ◽  
Subsequent Activation ◽  
Stimulation Of

In A7r5 vascular smooth muscle cells vasopressin, via arachidonic acid, regulates two Ca2+-entry pathways. Capacitative Ca2+ entry (CCE), activated by empty Ca2+ stores, is inhibited by arachidonic acid, and non-capacitative Ca2+ entry (NCCE) is stimulated by it. This reciprocal regulation ensures that all Ca2+ entry is via NCCE in the presence of vasopressin, while CCE mediates a transient Ca2+ entry only after removal of vasopressin. We demonstrate that type III NO synthase (NOS III) is expressed in A7r5 cells and that NO inhibits CCE. Inhibition of CCE by vasopressin requires NOS III and the requirement lies downstream of arachidonic acid. Activation of soluble guanylate cyclase by NO and subsequent activation of protein kinase G are required for inhibition of CCE. Stimulation of NCCE by vasopressin also requires NOS III, but the stimulation is neither mimicked by cGMP nor blocked by inhibitors of soluble guanylate cyclase or protein kinase G. We conclude that arachidonic acid formed in response to vasopressin stimulates NOS III. NO then directly stimulates Ca2+ entry through NCCE and, via protein kinase G, it inhibits CCE. The additional amplification provided by the involvement of guanylate cyclase and protein kinase G ensures that CCE will always be inhibited when vasopressin activates NCCE.

scholarly journals Calcineurin Directs the Reciprocal Regulation of Calcium Entry Pathways in Nonexcitable Cells

2003 ◽  
Vol 278 (41) ◽  
pp. 40088-40096 ◽  
Author(s):  
Olivier Mignen ◽  
Jill L. Thompson ◽  
Trevor J. Shuttleworth
Keyword(s):  
Calcium Entry ◽  
Reciprocal Regulation
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