Cytosolic calcium increase blocking

Manzamine A was able to block the cytosolic calcium increase induced by KCl depolarization on human neuroblastoma SH-SY5Y cells. The maximum effect was observed at 1.0 jxM, inhibiting by 31.5%. 8-Hydroxymanzamine A also showed a similar effect whereas manzamines E, F, and Y, ircinal A and weo-kauluamine did not show any significant effect [44]. In the B lymphocytes reaction assay hyrtiomanza-mine showed immunosuppressive activity with an EC50 of 2.0 xg/mL, but no activity was displayed against the KB human epidermoid carcinoma cell line [53]. 

Regarding human tissues, the few data available are contradictory, since according to some authors (Tedeschi et al., 1991) histamine release from basophils is not modified by H3 receptor ligands. In other studies (Bent et al., 1991), it was found that thioperamide could increase histamine release from adenoidal mast cells, but apparently (R)a-methylhistamine was totally inactive. In any case the concentrations of thioperamide are much higher than those necessary to block H3 receptors, thus suggesting that other mechanisms might be involved. Raible et al., (1994) hypothesized by the use of thioperamide, the presence of H3 receptors on human eosinophils which mediate histamine-induced increase in cytosolic calcium mobilization. However, the low efficacy of the known H3 receptor agonists, -as stimuli for eosinophils... 

Depolarization of vascular smooth muscle activates the L-type calcium channels, which results in increased cytosolic concentrations of calcium and hence increased tone. Calcium channel blockers (e.g., verapamil and diltiazem) block the influx of calcium through the L-type voltage-dependent channels located on vascular smooth muscle and cardiac muscle cells as well as cardiac nodal cells. Therefore, they are used in the treatment of angina, hypertension, and certain arrhythmias. 

The intracellular concentration of calcium plays an important role in maintaining the tone of smooth-muscle and in the contraction of the myocardium. Calcium enters muscle cells through special voltage-sensitive calcium channels. This triggers release of calcium from the sarcoplasmic reticulum and mitochondria, which further increases the cytosolic level of calcium. Calcium channel antagonists block... 

High levels of calcium-dependent cytosolic phospholipase A2 (CPLA2) activity have been reported to occur in rat and monkey spinal cords. At the cellular level, dense immunoreactivity is present in motor neurons from cervical, thoracic, lumbar, and sacral regions (Ong et al., 1999). Traumatic injury to spinal cord stimulates activities of lipases and phospholipases (Taylor et al., 1988). SCI significantly stimulates CPLA2 activity and its expression in injured spinal cord. This increase in CPLA2 activity can be blocked by the PLA2 inhibitor, mepacrine (Liu et al., 2006). 

The tributyltin benzoates were toxic to the K562 cellsJ Tributyltin benzoate (TBSB)-treated R562 cells showed a greater initial extracellular calcimn ion influx compared with the tributyltin halobenzoates. This is consistent with an early activation of endonucleases and DNA fragmentation in the TBSB-treated cells. This is also consistent with an earlier report by Chow et al. where the cytosolic-free calcimn ion concentration increases because of an extracellular calcium ion influx, an inhibition of the calcimn ion extrusion system, and the release of calcium from the intracellular reserves. These, and other studies, suggest involvement of nonspecific cation channels in the extracellular calcium ion influx that leads to an increase in observed cell viability. When the calcium channels were blocked with either verapamil or nefidipine, the extracellular calcium ion influx was partly inhibited and apotosis observed. 

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