ArticleJournal of cellular and molecular medicine2008
Functional effects of caloxin 1c2, a novel engineered selective inhibitor of plasma membrane Ca(2+)-pump isoform 4, on coronary artery.
Article in Journal of cellular and molecular medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 28 citations in OpenAlex.
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- Harnessing Hematopoietic Stem Cell Low Intracellular Calcium Improves Their Maintenance In Vitro.Cell stem cell · 2019Article
- Calcium transfer across the outer mantle epithelium in the Pacific oyster,Proceedings. Biological sciences · 2018Article
- Acute inhibition of PMCA4, but not global ablation, reduces blood pressure and arterial contractility via a nNOS-dependent mechanism.Journal of cellular and molecular medicine · 2018Article
- Identification of a receptor for extracellular renalase.PloS one · 2015Article
- Plasma membrane calcium ATPases as novel candidates for therapeutic agent development.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2013Review
- Use of allosteric targets in the discovery of safer drugs.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2013Review
- Distinct regulation of cytoplasmic calcium signals and cell death pathways by different plasma membrane calcium ATPase isoforms in MDA-MB-231 breast cancer cells.The Journal of biological chemistry · 2012Article
- Article
- Allosteric inhibitors of plasma membrane Ca pumps: Invention and applications of caloxins.World journal of biological chemistry · 2011Article
- Caloxins: a novel class of selective plasma membrane Ca2+ pump inhibitors obtained using biotechnology.Pflugers Archiv : European journal of physiology · 2008Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Coronary artery smooth muscle expresses the plasma membrane Ca(2+) pump (PMCA) isoforms PMCA4 and PMCA1. We previously reported the peptide inhibitor caloxin 1b1 that was obtained by using extracellular domain 1 of PMCA4 as the target (Am J Physiol Cell.290 [2006] C1341). To engineer inhibitors with greater affinity and isoform selectivity, we have now created a phage display library of caloxin 1b1-like peptides. We screened this library by affinity chromatography with PMCA from erythrocyte ghosts that contain mainly PMCA4 to obtain caloxin 1c2. Key properties of caloxin 1c2 are (a) Ki = 2.3 +/- 0.3 microM which corresponds to a 20x higher affinity for PMCA4 than that of caloxin 1b1 and (b) it is selective for PMCA4 since it has greater than 10-fold affinity for PMCA4 than for PMCA1, 2 or 3. It had the following functional effects on coronary artery smooth muscle: (a) it increased basal tone of the de-endothelialized arteries; the increase being similar at 10, 20 or 50 microM, and (b) it enhanced the increase in the force of contraction at 0.05 but not at 1.6 mM extracellular Ca(2+) when Ca(2+) extrusion via the Na(+)-Ca(2+) exchanger and the sarco/endoplasmic reticulum Ca(2+) pump were inhibited. We conclude that PMCA4 is pivotal to Ca(2+) extrusion in coronary artery smooth muscle. We anticipate caloxin 1c2 to aid in understanding the role of PMCA4 in signal transduction and home-ostasis due to its isoform selectivity and ability to act when added extracellularly.
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