D-myo-Inositol-1,4,6-phosphate (Ins(1,4,6)-P3) is a member of the inositol phosphate (InsP) family that play critical roles as small, soluble second messengers in the transmission of cellular signals. The most studied InsP, Ins(1,4,5)-P3, is a second messenger produced in cells by phospholipase C (PLC)-mediated hydrolysis of phosphatidylinositol-4,5-biphosphate. Binding of Ins(1,4,5)-P3 to its receptor on the endoplasmic reticulum results in opening of the calcium channels and an increase in intracellular calcium. Ins(1,4,6)-P3 (tested as the meso compound) is 9-fold less potent than Ins(1,4,5)-P3 at initiating Ca2+ release when injected into Xenopus oocytes.
D-myo-Inositol-4-phosphate (Ins(4)P1) is a member of the inositol phosphate (InsP) molecular family that play critical roles as small, soluble second messengers in the transmission of cellular signals. The most studied InsP, Ins(1,4,5)P3, is a second messenger produced in cells by phospholipase C (PLC)-mediated hydrolysis of phosphatidylinositol-4,5-diphosphate. Binding of Ins(1,4,5)P3 to its receptor on the endoplasmic reticulum results in opening of the calcium channels and an increase in intracellular calcium. Ins(4)P1 can be formed by dephosphorylation of Ins(1,4)P2 by inositol polyphosphate 1-phosphatase or dephosphorylated to inositol by inositol monophosphatase.
The phosphatidylinositol (PtdIns) phosphates represent a small percentage of total membrane phospholipids. However, they play a critical role in the generation and transmission of cellular signals. PtdIns-(1,2-dioctanoyl) is a synthetic analog of natural phosphatidylinositol (PtdIns) containing C8:0 fatty acids at the sn-1 and sn-2 positions. The compound features the same inositol and diacyl glycerol (DAG) stereochemistry as that of the natural compound. The short fatty acid chains of this analog, compared to naturally-occurring PtdIns, gives it different physical properties including high solubility in aqueous media. PtdIns are phosphorylated to mono- (PtdIns-P; PIP), di- (PtdIns-P2; PIP2), and triphosphates (PtdIns-P3; PIP3). Hydrolysis of PtdIns-(4,5)-P2 by phosphoinositide (PI)-specific phospholipase C generates inositol triphosphate (IP3) and DAG which are key second messengers in an intricate biochemical signal transduction cascade.
The phosphatidylinositol (PtdIns) phosphates represent a small percentage of total membrane phospholipids. However, they play a critical role in the generation and transmission of cellular signals. PtdIns-(3,4,5)-P3, also known as PIP3, is resistant to cleavage by PI-specific phospholipase C (PLC). Thus, it is likely to function in signal transduction as a modulator in its own right, rather than as a source of inositol tetraphosphates. PIP3 can serve as an anchor for the binding of signal transduction proteins bearing pleckstrin homology (PH) domains. Protein binding to PIP3 is important for cytoskeletal rearrangement and membrane trafficking. PtdIns-(3,4,5)-P3 (1,2-dihexanoyl) is a synthetic analog of natural PIP3 with C6:0 fatty acids at the sn-1 and sn-2 positions. The compound features the same inositol and diacylglycerol (DAG) stereochemistry as that of the natural compound. The short fatty acid chains of this analog give it different physical properties from naturally-occurring PIP3, including higher solubility in aqueous media.
The phosphatidylinositol phosphates represent a small percentage of total membrane phospholipids. However, they play a critical role in the generation and transmission of cellular signals. PtdIns-(3,4,5)-P3 can serve as an anchor for the binding of signal transduction proteins bearing pleckstrin homology (PH) domains. Centuarin α and the Akt-family of GTPase activating proteins are examples of PtdIns-(3,4,5)-P3-binding proteins. Protein-binding to PtdIns-(3,4,5)-P3 is important for cytoskeletal rearrangements and membrane trafficking. PtdIns-(3,4,5)-P3 is resistant to cleavage by PI-specific phospholipase C (PLC). Thus, it is likely to function in signal transduction as a modulator in its own right, rather than as a source of inositol tetraphosphates. For further reading on inositol phospholipids, see also references and .
The phosphatidylinositol (PtdIns) phosphates represent a small percentage of total membrane phospholipids. However, they play a critical role in the generation and transmission of cellular signals. PtdIns-(4)-P1 (1,2-dioctanoyl) is a synthetic analog of natural phosphatidylinositol (PtdIns) featuring C8:0 fatty acids at the sn-1 and sn-2 positions. The compound contains the same inositol and diacylglycerol (DAG) stereochemistry as the natural compound. PtdIns-(4)-P1 can be phosphorylated to di- (PtdIns-P2; PIP2) and triphosphates (PtdIns-P3; PIP3). Hydrolysis of PtdIns-(4,5)-P2 by phosphoinositide (PI)-specific phospholipase C generates inositol triphosphate (IP3) and DAG which are key second messengers in an intricate biochemical signal transduction cascade.
Tetranactin is a macrotetrolide and a monovalent cation ionophore that has been found in S. aureus and has antibacterial, insecticidal, and mitogenic activities. It exhibits an equilibrium permeability ratio 1,000-fold greater for lithium than sodium or cesium ions accross bilayer membranes at low voltages. Tetranactin inhibits the growth of Gram-positive bacteria and C. miyabeanus and R. solani fungi when used at concentrations less than 0.9 μg/ml. Tetranactin (0.5-1.5 μg per insect) dose-dependently increases the mortality of adult C. chinensis weevils up to 100% and has mitogenic activity against T. telarius when sprayed onto plants with an LC50 value of 9.2 μg/ml. It reduces IL-1β- and cAMP-induced secretion of phospholipase A2 (PLA2) from rat mesangial cells (IC50s = 43 and 33 nM, respectively). Tetranactin (50 ng/ml) suppresses the proliferation of human T lymphocytes induced by allogeneic cells and IL-2 and supresses the generation of cytotoxic T lymphocytes in mixed lymphocyte cultures. In vivo, tetranactin (10 mg/animal per day) completely inhibits the formation of experimental autoimmune uveoretinitis (EAU) in rats.
Ins(1,2)P2 (sodium salt) is one of the many inositol phosphate (InsP) isomers that could act as small, soluble second messengers in the transmission of cellular signals. The most studied InsP Ins(1,4,5)P3, is a second messenger produced in cells by phospholipase C (PLC)-mediated hydrolysis of phosphatidylinositol-4,5-biphosphate. Binding of Ins(1,4,5)P3 to its receptor on the endoplasmic reticulum results in opening of the calcium channels and an increase in intracellular calcium. Ins(1,2)P2 (tested as the D L racemic mixture) is ~1,000-fold less potent than Ins(1,4,5)P3 at initiating Ca2+ release when injected into Xenopus oocytes.
D-myo-Inositol-1,3-phosphate (Ins(1,3)P) is a member of the inositol phosphate (InsP) molecular family that play critical roles as small, soluble second messengers in the transmission of cellular signals. The most studied InsP, Ins(1,4,5)P3 is a second messenger produced in cells by phospholipase C (PLC)-mediated hydrolysis of phosphatidylinositol-4,5-biphosphate. Binding of Ins(1,4,5)P3 to its receptor on the endoplasmic reticulum results in opening of the calcium channels and an increase in intracellular calcium. Ins(1,3)P2 can be dephosphorylated to Ins(1)P by inositol polyphosphate 3-phosphatase and further dephosphorylated to inositol by inositol monophosphatase.
Phosphatidylcholine (PC) species are a common class of phospholipids that comprise the mammalian cell membrane. 1,2-Dioctanoyl PC is a synthetic analog of natural phosphatidylcholine species containing saturated C8:O fatty acids in the sn-1 and sn-2 positions of the glycerol backbone. It exhibits a critical micelle concentration (CMC) value of 0.25 mM at 27°C. 1,2-Dioctanoyl PC serves as an efficient substrate for phospholipase D (PLD) as well as sPLA2 isozymes from bovine pancreas and bee venom.
p-Nitrophenylphosphorylcholine is a chromogenic substrate that is used to measure phospholipase C (PLC) activity. Hydrolysis of p-nitrophenylphosphorylcholine by PLC results in the liberation of p-nitrophenol, which can be measured at 405 nm at pH 7.2-7.5.