Caloxin 1B1

Product Name: Caloxin 1B1

Sequence One Letter Code: TAWSEVLHLLSRGGG

Sequence Three Letter Code: H-Thr-Ala-Trp-Ser-Glu-Val-Leu-His-Leu-Leu-Ser-Arg-Gly-Gly-Gly-OH

Chemical Formula:C70H111N21O21

Molecular Weight: 1582.9

Purity: 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: Cardiovascular Disease Research

Conjugation: Unconjugated

Code Nacres: NA.26

Application: Caloxin 1B1 is a peptide inhibitor identified through screening for ligands that bind to extracellular domain 1 of plasma membrane Ca²⁺-ATPase 4 (PMCA4), a key enzyme responsible for maintaining cellular calcium homeostasis by exporting Ca²⁺ from the cytosol. The peptide selectively inhibits PMCA activity from the extracellular side of the membrane and shows greater affinity for the PMCA4 isoform compared with PMCA1. Because Caloxin 1B1 targets an extracellular region of the pump, it can be applied directly to intact cells or tissues without the need for membrane permeabilization. This property makes it particularly useful for studying calcium transport regulation in physiological systems. Caloxin 1B1 has been widely used in research on smooth muscle contractility, endothelial cell signaling, and cardiovascular physiology, as well as in investigations of isoform-specific PMCA function and calcium-dependent cellular signaling pathways.

Current Research: Calcium ions (Ca²⁺) serve as universal intracellular messengers that regulate a wide range of biological processes, including muscle contraction, neurotransmitter release, gene expression, and cell proliferation. Because calcium signaling must be tightly controlled, cells rely on specialized transport systems to regulate cytosolic Ca²⁺ levels. One of the most important components of this regulatory network is the plasma membrane Ca²⁺-ATPase (PMCA) family, which actively exports calcium from the cytoplasm to maintain low intracellular Ca²⁺ concentrations. Among the PMCA isoforms, PMCA4 has attracted significant attention due to its involvement in cardiovascular physiology and calcium-dependent signaling pathways. The peptide Caloxin 1B1 has emerged as a valuable experimental tool for studying PMCA function, particularly because it selectively inhibits the pump from the extracellular side of the membrane. Plasma Membrane Ca²⁺-ATPases and Calcium Homeostasis PMCA enzymes are ATP-dependent transporters located in the plasma membrane that remove Ca²⁺ from the cytosol by pumping it into the extracellular space. This activity is essential for restoring basal calcium levels after signaling events and preventing toxic accumulation of intracellular calcium. Four major PMCA isoforms (PMCA1–4) have been identified in mammals. Although these isoforms share structural similarities, they exhibit distinct tissue distributions and regulatory properties. PMCA1 is widely expressed and generally considered a housekeeping isoform responsible for maintaining basal calcium levels. In contrast, PMCA4 is particularly prominent in specialized tissues such as the cardiovascular system and plays roles in regulating localized calcium signaling domains. Because calcium signaling influences numerous cellular processes, PMCA activity directly affects cellular excitability, contractility, and signal transduction pathways. Identification and Design of Caloxin Peptides To investigate PMCA function more precisely, researchers have developed peptide inhibitors known as caloxins. These peptides were identified through screening strategies aimed at discovering ligands that bind to extracellular domains of PMCA proteins. Caloxin 1B1 was discovered as a peptide capable of interacting with extracellular domain 1 of PMCA4. By binding to this region, the peptide interferes with the pump’s ability to transport calcium ions, thereby inhibiting its activity. One of the notable features of Caloxin 1B1 is its isoform preference. The peptide shows greater inhibitory activity toward PMCA4 compared with PMCA1, making it useful for investigating isoform-specific functions of calcium pumps. Extracellular Mode of Action Most inhibitors targeting membrane transport proteins require access to intracellular domains or catalytic sites located within the cytoplasm. In contrast, Caloxin 1B1 interacts with an extracellular region of PMCA, allowing the inhibitor to function without crossing the cell membrane. This extracellular mode of action offers several practical advantages. Because the peptide does not need to enter the cell, it can be applied directly to intact cells, tissues, or organ preparations. Researchers can therefore manipulate PMCA activity in physiological systems without the need for chemical permeabilization or invasive delivery methods. This property makes Caloxin 1B1 particularly valuable in studies that aim to preserve native cellular architecture and signaling environments. Applications in Calcium Signaling Research Caloxin 1B1 is widely used as a tool for exploring the role of PMCA in calcium transport and cellular signaling. By selectively inhibiting calcium extrusion from the plasma membrane, the peptide allows researchers to examine how changes in calcium handling influence intracellular signaling pathways. Experimental applications often involve measuring changes in cytosolic calcium levels, calcium oscillations, or downstream signaling responses following PMCA inhibition. These studies help clarify how PMCA contributes to shaping calcium signals that regulate physiological functions. Role in Smooth Muscle and Cardiovascular Physiology One area where Caloxin 1B1 has proven particularly useful is the study of smooth muscle contractility. Smooth muscle contraction is regulated by intracellular calcium concentration, which influences actin–myosin interactions and cellular tension. By inhibiting PMCA activity, Caloxin 1B1 can alter calcium dynamics within smooth muscle cells, providing insight into how calcium export mechanisms contribute to vascular tone and contractile regulation. The peptide has also been applied in cardiovascular research, where calcium signaling plays a crucial role in endothelial function and cardiac physiology. PMCA4, in particular, has been implicated in signaling complexes that regulate nitric oxide production and vascular responses. Investigating Isoform-Specific PMCA Functions Because PMCA isoforms can perform distinct roles in different tissues, understanding their individual contributions is important for deciphering calcium signaling networks. Caloxin 1B1 provides a means of examining isoform-specific PMCA activity, especially in systems where PMCA4 is the dominant form. Using this peptide inhibitor, researchers can selectively modulate PMCA4 activity and analyze how this affects cellular processes such as signal transduction, contractility, and calcium-dependent enzyme activation. A Tool for Studying Calcium Transport Regulation Caloxin 1B1 represents an important reagent for investigating membrane calcium transport and calcium-dependent cellular regulation. Its ability to bind an extracellular region of PMCA allows direct application to intact biological systems while maintaining physiological conditions. By selectively inhibiting PMCA4 activity, the peptide supports research into calcium homeostasis, smooth muscle physiology, endothelial signaling, and cardiovascular function. As studies continue to uncover the complexity of calcium signaling networks, tools such as Caloxin 1B1 remain valuable for dissecting the mechanisms that control intracellular calcium dynamics and their impact on cellular behavior.