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2016 Jun 01;51-2:92-99. doi: 10.1166/msr.2016.1050.
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Carvedilol inhibits cADPR- and IP3-induced Ca2+ release.
Morgan AJ
,
Bampali K
,
Ruas M
,
Factor C
,
Back TG
,
Chen SRW
,
Galione A
.
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Spontaneous Ca2+ waves, also termed store-overload-induced Ca2+ release (SOICR), in cardiac cells can trigger ventricular arrhythmias especially in failing hearts. SOICR occurs when RyRs are activated by an increase in sarcoplasmic reticulum (SR) luminal Ca2+. Carvedilol is one of the most effective drugs for preventing arrhythmias in patients with heart failure. Furthermore, carvedilol analogues with minimal β-blocking activity also block SOICR showing that SOICR-inhibiting activity is distinct from that for β-block. We show here that carvedilol is a potent inhibitor of cADPR-induced Ca2+ release in sea urchin egg homogenate. In addition, the carvedilol analog VK-II-86 with minimal β-blocking activity also suppresses cADPR-induced Ca2+ release. Carvedilol appeared to be a non-competitive antagonist of cADPR and could also suppress Ca2+ release by caffeine. These results are consistent with cADPR releasing Ca2+ in sea urchin eggs by sensitizing RyRs to Ca2+ involving a luminal Ca2+ activation mechanism. In addition to action on the RyR, we also observed inhibition of inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release by carvedilol suggesting a common mechanism between these evolutionarily related and conserved Ca2+ release channels.
Berridge,
The versatility and universality of calcium signalling.
2000, Pubmed
Berridge,
The versatility and universality of calcium signalling.
2000,
Pubmed
Calcraft,
NAADP mobilizes calcium from acidic organelles through two-pore channels.
2009,
Pubmed
Chen,
The ryanodine receptor store-sensing gate controls Ca2+ waves and Ca2+-triggered arrhythmias.
2014,
Pubmed
Clapper,
Pyridine nucleotide metabolites stimulate calcium release from sea urchin egg microsomes desensitized to inositol trisphosphate.
1987,
Pubmed
,
Echinobase
Fan,
Gating machinery of InsP3R channels revealed by electron cryomicroscopy.
2015,
Pubmed
Galione,
Ca(2+)-induced Ca2+ release in sea urchin egg homogenates: modulation by cyclic ADP-ribose.
1991,
Pubmed
,
Echinobase
Galione,
Cyclic ADP-ribose and the regulation of calcium-induced calcium release in eggs and cardiac myocytes.
1998,
Pubmed
,
Echinobase
Galione,
Redundant mechanisms of calcium-induced calcium release underlying calcium waves during fertilization of sea urchin eggs.
1993,
Pubmed
,
Echinobase
Hisatsune,
IP3 receptor mutations and brain diseases in human and rodents.
2017,
Pubmed
Iino,
Actions of cADP-ribose and its antagonists on contraction in guinea pig isolated ventricular myocytes. Influence of temperature.
1997,
Pubmed
,
Echinobase
Jaffe,
Fast calcium waves.
2010,
Pubmed
Kannt,
Selective inhibitors of cardiac ADPR cyclase as novel anti-arrhythmic compounds.
2012,
Pubmed
Knollmann,
Casq2 deletion causes sarcoplasmic reticulum volume increase, premature Ca2+ release, and catecholaminergic polymorphic ventricular tachycardia.
2006,
Pubmed
Lee,
Structural determination of a cyclic metabolite of NAD+ with intracellular Ca2+-mobilizing activity.
1989,
Pubmed
,
Echinobase
Lee,
Potentiation of calcium- and caffeine-induced calcium release by cyclic ADP-ribose.
1993,
Pubmed
,
Echinobase
Lee,
Mechanisms of calcium signaling by cyclic ADP-ribose and NAADP.
1997,
Pubmed
,
Echinobase
Lee,
Specific binding of cyclic ADP-ribose to calcium-storing microsomes from sea urchin eggs.
1991,
Pubmed
,
Echinobase
McPherson,
Cortical localization of a calcium release channel in sea urchin eggs.
1992,
Pubmed
,
Echinobase
Meissner,
Purification and reconstitution of the ryanodine- and caffeine-sensitive Ca2+ release channel complex from muscle sarcoplasmic reticulum.
1991,
Pubmed
Missiaen,
Spontaneous calcium release from inositol trisphosphate-sensitive calcium stores.
1991,
Pubmed
Morgan,
The luminal Ca(2+) chelator, TPEN, inhibits NAADP-induced Ca(2+) release.
2012,
Pubmed
,
Echinobase
Morgan,
Preparation and use of sea urchin egg homogenates.
2014,
Pubmed
,
Echinobase
Palade,
Spontaneous calcium release from sarcoplasmic reticulum. General description and effects of calcium.
1983,
Pubmed
Patel,
Function and dysfunction of two-pore channels.
2015,
Pubmed
Rakovic,
An antagonist of cADP-ribose inhibits arrhythmogenic oscillations of intracellular Ca2+ in heart cells.
1999,
Pubmed
Roderick,
Calcium-induced calcium release.
2003,
Pubmed
Roderick,
Pacemaking, arrhythmias, inotropy and hypertrophy: the many possible facets of IP3 signalling in cardiac myocytes.
2007,
Pubmed
Seo,
Structural and functional conservation of key domains in InsP3 and ryanodine receptors.
2012,
Pubmed
Smith,
Novel carvedilol analogues that suppress store-overload-induced Ca2+ release.
2013,
Pubmed
Venturi,
From eggs to hearts: what is the link between cyclic ADP-ribose and ryanodine receptors?
2012,
Pubmed
,
Echinobase
Walseth,
Synthesis and characterization of antagonists of cyclic-ADP-ribose-induced Ca2+ release.
1993,
Pubmed
,
Echinobase
Walseth,
Identification of cyclic ADP-ribose-binding proteins by photoaffinity labeling.
1993,
Pubmed
,
Echinobase
Zhang,
Identifying Glyceraldehyde 3-Phosphate Dehydrogenase as a Cyclic Adenosine Diphosphoribose Binding Protein by Photoaffinity Protein-Ligand Labeling Approach.
2017,
Pubmed
Zhou,
Carvedilol and its new analogs suppress arrhythmogenic store overload-induced Ca2+ release.
2011,
Pubmed
