Intracellular calcium levels

The behavior of calcium in the cells can be considered as a metabolic process. There is uptake, distribution, and excretion of calcium in the cells. The uptake of calcium occurs via activation of calcium channels. The end result is elevation of intracellular calcium levels and subsequent activation. Be-... 

Dopp E, voLLMER G, HAHNEL c, GREVESMUHL Y and SCHIFFMANN D (1999) Modulation of tile intracellular calcium level in mammalian cells caused by ivp-estradiol, different phytoestrogens and the anti-estrogen ICl 182780. JSteroid Biochem Mol Biol. 68 (1-2) 57-64. 

Regulation of glycogen synthesis and degradation is essentially the same in the liver and muscle, but there are a couple of wrinkles. Glycogen degradation is also activated in muscle in response to the rise in intracellular calcium levels that accompanies contraction. This is achieved by... 

In many cells, phosphoinositide signaling leads to an elevation in intracellular calcium levels through the release of calcium from intracellular stores in response to IP3-dependent gating of channels in the endoplasmic epithelium (Ch. 20). It is not known if IP3 plays a critical role in TRC transduction, but such a role would be consistent with recent findings that a Ca2+-activated cation channel, TRPM5, is essential for normal sweet, bitter and umami taste function [49,66-69],... 

Results of in vitro studies suggest an interaction between calcium ions and cyanide in cardiovascular effects (Allen and Smith 1985 Robinson et al. 1985a). It has been demonstrated that exposure to cyanide in metabolically depleted ferret papillary muscle eventually results in elevated intracellular calcium levels, but only after a substantial contracture develops (Allen and Smith 1985). The authors proposed that intracellular calcium may precipitate cell damage and arrhythmias. The mechanism by which calcium levels are raised was not determined. Franchini and Krieger (1993) produced selective denervation of the aortic and carotid bifurcation areas, and confirmed the carotid body chemoreceptor origin of cardiovascular, respiratory and certain behavioral responses to cyanide in rats. Bradycardia and hyperventilation induced by cyanide are typical responses evoked by carotid body chemoreceptor stimulation (Franchini and Krieger 1993). 

While ionophore-stimulated 5-LO product release from neutrophils is often used as an indication of 5-LO inhibition, one must interpret these results cautiously. For example, halothane, an inhalation anaesthetic which may cause membrane perturbation [26], and colchicine, a microtubule disrupter [27], both were active, but presumably not because of 5-LO inhibition. A23187 is assumed to stimulate 5-LO by raising the intracellular calcium level, but this agent causes many other effects which may or may not be related to 5-LO activation, including changes in membrane potential, protein phosphorylation, phospholipid turnover, cyclic nucleotide levels, and DNA and protein synthesis [28]. Also, the effects of some putative 5-LO inhibitors on product release from neutrophils has been shown to vary with the stimulant used [29]. 

Mitochondria are the ATP suppliers of the cells and have an important role in modulating intracellular calcium levels and cellular apoptosis. The mitochondrial respiratory chain is furthermore an important suppher of damaging free radicals. Evidence increases that mitochondria are heavily involved in numerous diseases and therefore they may become important targets for the development of new drugs and therapies [47]. 

Cheng B, McMahon DG, Mattson MP Modulation of calcium current, intracellular calcium levels and cell survival by glucose deprivation and growth factors in hippocampal neurons. Brain Res 607 275-285, 1993 Cheng CHK, Costall B, Kelly ME, et al Actions of 5-hydroxytryptophan to inhibit and disinhibit mouse behaviour in the hght dark test. Eur J Pharmacol 255 39-49, 1994... 

NO has a significant effect on vascular smooth muscle tone and blood pressure. Numerous endothelium-dependent vasodilators, such as acetylcholine and bradykinin, act by increasing intracellular calcium levels, which induces NO synthesis (Figure 19-2). Mice with a knockout mutation in the eNOS gene display increased vascular tone and elevated mean arterial pressure, indicating that eNOS is a fundamental regulator of blood pressure. The effects of vasopressor drugs are increased by inhibition of NOS. 

The drug indirectly alters the regulation of intracellular calcium levels via protein kinase C and can alter the transcription of gene- (downregulating) encoding enzymes (e.g., ATP/ADP translocase) and those involved in energy production and specific for cardiac tissue. 

Brownson D. M., Mabry T. J., and Leslie S. W. (2002). The cycad neuiotoxic amino acid, fi-N-methylamino-l-alanine (BMAA), elevates intracellular calcium levels in dissociated rat brain cells. J. Ethnopharmacol. 82 159-167. 

The formation of the neurite-like processes appears to be dependent on assembly of microtubules as colchicine and Colcemid, antimicrotubule drugs, prevented shape changes in the presence of butyrate (2,8). The amount of tubulin per cell did not change when HeLa were treated with butyrate (R.C.Henneberry, unpublished observations). The role of microtubule assembly was further explored with a calcium ionophore which alters intracellular calcium levels and thus promotes microtubule depolymerization. 

NaCIO is an acknowledged novel absorption enhancer for ampicillin sodium [99], glycyr-rhizin [100,101], gentamicin [102], phenoxymethyl penicillin [103], cefoxitin sodium [104,105], and acyclovir [106], Takahashi et al. [107] reported that the enhanced membrane permeability of phenolsulfonphthalein depends on the disappearance kinetics of CIO from the loop and its calcium ion sequestration capacity. The enhancing mechanisms of NaCIO are proposed to be involved in (1) Ca2+ sequestration, (2) increase in pore size and solvent drag, (3) interaction with membrane proteins and lipids, and (4) increase in the intracellular calcium level [104,105,108-111],... 

The expression of genes involved in cell proliferation and cell death is regulated by nuclear transcriptional factors. NFAT (Nuclear Factor of Activated T cells) proteins are a family of Ca2+-dependent transcription factors (Crabtree, 2001), whose nuclear translocation and transcriptional activity is regulated by Ca2+/calmodulin-dependent protein phosphatase, calcineurin (Crabtree, 2001). Thus, NFAT proteins can potentially be activated by diverse stimuli that lead to increased intracellular calcium levels. The NF-kB (nuclear factor kappa B) family... 

Preliminary studies also suggested that calcium channel blockers my increase the risk of cancer.10,28 Intracellular calcium levels are important in regulating cell division. By modifying calcium influx, calcium channel blockers could conceivably accelerate cell proliferation and lead to cancerous growths. Fortunately, the carcinogenic potential of these drugs has not been proven conclusively by subsequent studies.21 Hence, calcium channel blockers continue to be used cautiously but effectively in large numbers of patients. 

Digoxin (Lanoxin] Digitioxin (Digitaline] Increase myocardial contractility by elevating intracellular calcium levels and facilitating actin-myosin interaction in cardiac cells may also help normalize autonomic effects on the heart... 

Other positive inotropes Inamrinone (generic] Milrinone (Primacor] Enhance myocardial contractility by prolonging effects of cyclic adenosine monophosphate (cAMP], which increases intracellular calcium levels and promotes stronger actin-myosin interaction in cardiac cells... 

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