Calcium mobilizing agents

A precursor in the synthesis of a promising calcium sensitizing agent from E. Merck [33], a chiral thiadiazin-2-one EMD 53986, 3,6-Dihydro-5-[l,2,3,4-tetrahy-dro-6-quinolyl]-6-methyl-2H-l,3,4-thiadiazin-2-one [26]. The study was performed using Celluspher , a CSP prepared from cellulose tri(p-methylbenzoate) according to a patent from Ciba-Geigy [34]. The spherical particles had a mean particle diameter of 20 3 pm and the mobile phase was pure methanol. 

G. L. Rossi, D. J. Young, S. I. Wasserman, and K. E. Barrett, Calcium mobilization in activated mast cells monitored by flow cytometric analysis. Agents Actions 31, 257-262 (1990). 

Further studies have revealed that pumiliotoxin B interacts with voltage-dependent sodium channels to elicit an increased influx of sodium ions (101,102) and, in brain and heart preparations, a stimulation of phosphoino-sitide breakdown (101,103-106). The phosphoinositide breakdown can, via inositol trisphosphate, cause release of calcium from internal storage sites. The cardiotonic activity of pumiliotoxin B and various congeners and synthetic analogs correlates well with the stimulation of phosphoinositide breakdown (104,105). A number of studies on stimulation of sodium uptake by pumiliotoxin B and inhibition by local anesthetics and other agents have appeared (106-108). The effects of pumiliotoxin B on neuromuscular preparations have been reinterpreted as due primarily to effects on sodium channels, although additional direct effects on calcium mobilization remain possible (109). It has recently been proposed that pumiliotoxin B enhances the rate of activation of sodium channels (110). One characteristic effect of pumiliotoxin B is to elicit repetitive firing in neurons, apparently because of effects on sodium channel function (109-111). 

Thastrup O, Foder B, and Scharff O. (1987). The calcium mobilizing tumor promoting agent, thapsigargin, elevates the platelet cytoplasmic free calcium concentration to a higher steady state level. A possible mechanism of action for the tumor promotion. Biochem Biophys. Res. Commun. 142,654-660. 

Kosower, N.S., Glaser, T. and Kosower, E.M. (1983) Membrane-mobility agent-promoted fusion of erythrocytes fusibility is correlated with attack by calcium-activated cytoplasmic proteases on membrane proteins. Proc. Natl. Acad. Sci. USA 80 7542-7546. 

ADP-ribosylation reactions such as DNA repair, calcium mobilization and deacetylation (Kirkland 2009). In addition, at pharmacological concentrations, niacin is an effective agent for the treatment of dislipidemias and atherosclerosis (Prousky et al. 2011). Furthermore, evidence exists that niacin ameliorates acute migraine, chronic tension-type headaches, depression and schizophrenia (Prousky et al. 2011). This chapter focuses on chemical and biochemical aspects of the vitamin. 

Urinary lead levels have also been used to measure current exposure (Robinson 1974) but they are of questionable value as biomarkers of exposure because of the relatively low and fluctuating lead levels that are excreted in the urine (ACGIH 1986 Ibels and Pollock 1986 Jensen 1984). In contrast, the determination of urinary lead following a single injection of the chelating agent, calcium disodium EDTA, which mobilizes extracellular lead and produces increased urinary excretion of lead, is presumed to be indicative of an elevated body burden of lead (Cory-Slechta et al. 1987 Ibels and Pollock 1986 Janin et al. 1985). Children whose PbB levels are 45 pg/dL should not receive a provocative chelation... 

A second way to improve resolution is the modification of mobility by complexation of the analyte. Many buffers for analysis of cations use HIBA or 18-crown-6 to improve the resolution between sodium, potassium, calcium, magnesium, etc. as well as some aliphatic amines. By diluting an existing validated buffer, one can change the concentration of the complexation agent and thus also the selectivity of the system. 

The calcium-phosphoinositide and cAMP signaling pathways oppose one another in some cells and are complementary in others. For example, vasopressor agents that contract smooth muscle act by IP3-mediated mobilization of Ca2+, whereas agents that relax smooth muscle often act by elevation of cAMP. In contrast, cAMP and phosphoinositide second messengers act together to stimulate glucose release from the liver. 

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