Sasamori, Kan, Tsukasa Sasaki, Shin Takasawa, Tsutomu Tamada, Masayuki Nara, Toshiya Irokawa, Sanae Shimura, Kunio Shirato, and Toshio Hattori. Cyclic ADP-ribose, a putative Ca -mobilizing second messenger, operates in submucosal gland acinar cells. Am J Physiol Lung Cell Mol Physiol 287: L69–L78, 2004. First published February 27, 2004; 10.1152/ajplung.00454. 2003.—Cyclic ADP-ribose (cADPR), a...

Binding of IP3 (inositol 1,4,5-trisphosphate) to the IP3-binding core (residues 224-604) of IP3Rs (IP3 receptors) initiates opening of these ubiquitous intracellular Ca2+ channels. The mechanisms are unresolved, but require conformational changes to pass through the suppressor domain (residues 1-223). A calmodulin-binding peptide derived from myosin light chain kinase uncouples these events. We...

The resistance of inositol 1,4,5-trisphosphate receptor (IP3R)-deficient cells to multiple forms of apoptosis demonstrates the importance of IP3-gated calcium (Ca2+) release to cellular apoptosis. However, the specific upstream biochemical events leading to IP3-gated Ca2+ release during apoptosis induction are not known. We have shown previously that the cyclin-dependent kinase 1/cyclin B (cdk1...

Sulfhydryl reagents such as tert-butyl hydroperoxide (TBHP) have been shown to increase cytosolic Ca2+ concentration ([Ca2+]i) in rat hepatocytes in a way that resembles responses to Ca(2+)-mobilizing hormones (Saikada, I., Thomas, A. P., and Farber, J. L. (1991) J. Biol. Chem. 266, 717-722; Rooney, T. A., Renard, D. C., Sass, E. J., and Thomas, A. P. (1991) J. Biol. Chem. 266, 12272-12282) and...

IP3 receptors are channels that mediate the release of Ca(2+) from the intracellular stores of cells stimulated by hormones or neurotransmitters. Adenophostin A (AdA) is the most potent agonist of IP3 receptors, with the β-anomeric adenine contributing to the increased potency. The potency of AdA and its stability towards the enzymes that degrade IP3 have aroused interest in AdA analogs for bio...

Angiopoietin-1 (Ang1) exerts a vascular endothelial barrier protective effect by blocking the action of permeability-increasing mediators such as vascular endothelial growth factor (VEGF) through unclear mechanisms. Because VEGF may signal endothelial hyperpermeability through the phospholipase C (PLC)-IP3 pathway that activates extracellular Ca entry via the plasmalemmal store-operated channel...

We have attempted to provide evidence for the production of inositol phosphate (IP) metabolites as an indication of specific receptor-mediated signal transduction in human peripheral blood lymphocytes (PBL) in response to interleukin-8 (IL-8). IP metabolites were measured, after loading of PBL with [3H]-D-myo-inositol, by anion exchange high-performance liquid chromatography (HPLC) and liquid s...

Epidermal growth factor (EGF) exhibits specific saturable binding to cultured rat inner medullary collecting tubule cells and stimulates inositol trisphosphate (IP3) production by these cells in a dose-dependent fashion. EGF-stimulated IP3 production is enhanced by GTP-ys or AJF4 and is inhibited by GDPBs or pertussis toxin. Alterations in extracellular Ca2" have no effect on either basal or EG...

In this study, we have showed that aortic endothelial cells (GM7372A cell line) express CD44v10 [a hyaluronan (HA) receptor], which is significantly enriched in cholesterol-containing lipid rafts (characterized as caveolin-rich plasma membrane microdomains). HA binding to CD44v10 promotes recruitment of the cytoskeletal protein, ankyrin and inositol 1,4,5-triphosphate (IP3) receptor into choles...

Activated phospholipase C (PLC*) generates 1,4,5-triphosphate (IP3) and diacylglycerol (DAG) from phosphatidyl inositol (PIP2). The DAG remains in the plasma membrane and co-activates conventional protein kinase C (PKC) with Ca2+. We have developed a mathematical model for the activation of the Ca2+-dependent PKC and its negative feedback on phospholipase C (PLC) and coupled it to the De Young-...