Ca2+ fluxes

Chemokines, a superfamily of small (8 to 14 kd) chemoattractant cytokines, were originally identified by their capacity to mediate gradient-dependent cell migration, accompanied by Ca2+ flux, in vitro. Sequence homology of mammal, bird, and fish chemokines indicates that this family of proteins is highly conserved throughout evolution. Chemokines are multifunctional molecules with a vast repertoire of specialized functions in different organs. Broadly, chemokine actions are associated with cell adhesion, cytokine secretion, cellular... 

JA Williamson, JR Monack. (1989). Hormone effects on cellular Ca2+ fluxes. Annu Rev Physiol 51 107-124. 

Cross-reactivity with JAK kinases is a recurring theme with pyrimidine-carboxamides [81,82], but compound 20 exemplifies a Syk-selective series [81]. Pyrimidine amide 20 has an IC50 of 6nM against Syk, and broad screening (at 300 nM concentration) demonstrated significant selectivity for Syk over 270 kinases. In Ramos cells, 20 inhibited BCR-induced phosphorylation of BLNK, a direct substrate of Syk, with an EC50 of 500-750 nM and Ca2+ flux with an EC50 = 117 nM. Compound 20 potently... 

To what extent does the SR contribute to the rise of [Ca2+]j that activates contraction In other words, what are the relative contributions of the SR and the surface membrane In contrast to the situation in striated muscle where inhibition of SR function abolishes most of contraction, there are several examples in smooth muscle of large amounts of force remaining under these conditions. The SR is an intracellular store of finite capacity. Release of Ca2+ from such a store is well suited to producing transient contractions. However, maintained contraction can be produced by steady state changes in Ca2+ fluxes across the surface membrane. Does the SR make different contributions during different phases of contraction ... 

Most work on the SR and diseased smooth muscle has concerned vascular smooth muscle in hypertensive animals, and bladders from animal models of outflow obstruction. The tools used to study SR function are mainly indirect, and include recording tension or intracellular [Ca2+] with fluorescent probes, measuring Ca2+ fluxes with 45Ca, and investigating the effects of drugs known to block SERCA or activate store release. More directly, some measurement of the activity of SERCA in microsomal preparations has been undertaken (e.g. Zderic et al 1996). 

Since there is such a great difference between the external and internal (or at least cytosolic) Ca2+ levels, and since cytosolic Ca2+ levels below micromolar must be maintained to allow the signalling role of Ca2+ fluxes, it is clear that in order to maintain intracellular Ca2+ homeostasis, all cells must have developed mechanisms for regulating both Ca2+ uptake and egress, which are described in the next sections. 

Initial biochemical studies indicate that agonist binding was regulated by guanyl nucleotides, implying that the receptor belongs to the superfamily of receptors coupled to G proteins. In addition, various intracellular responses were found to be associated with Hi-receptor stimulation inositol phosphate release, increase in Ca2+ fluxes, cyclic AMP or cyclic GMP accumulation in whole cells and arachidonic acid release [1],... 

Burdakov D., and Verkhratsky A. 2006 Biophysical re-equilibration of Ca2+ fluxes as a simple biologically plausible explanation for complex intracellular Ca2+ release patterns. FEBS Lett 380, 463-468. 

Cameron, A. M., Steiner, J. P., Roskams, A. J., Ali, S. M., Ronnett, G. V., and Snyder, S. H. (1995b). Calcineurin associated with the inositol 1,4,5-trisphosphate receptor-FKBP12 complex modulates Ca2+ flux. Cell83, 463-472. 

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