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Echinobase
ECB-ART-45660
Messenger (Los Angel) 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 .


Abstract
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.

PubMed ID: 28758053
PMC ID: PMC5531262
Article link: Messenger (Los Angel)
Grant support: [+]

Genes referenced: LOC100887844

References [+] :
Berridge, The versatility and universality of calcium signalling. 2000, Pubmed