Inhibition by calcium

Zhang, Y., Gupta, A., Wang, H., et al. (2005) BCRP transports dipyridamole and is inhibited by calcium channel blockers. Pharm. Res. 22, 2023-2034. 

Orotic acid in the diet (usually at a concentration of 1 per cent) can induce a deficiency of adenine and pyridine nucleotides in rat liver (but not in mouse or chick liver). The consequence is to inhibit secretion of lipoprotein into the blood, followed by the depression of plasma lipids, then in the accumulation of triglycerides and cholesterol in the liver (fatty liver) [141 — 161], This effect is not prevented by folic acid, vitamin B12, choline, methionine or inositol [141, 144], but can be prevented or rapidly reversed by the addition of a small amount of adenine to the diets [146, 147, 149, 152, 162]. The action of orotic acid can also be inhibited by calcium lactate in combination with lactose [163]. It was originally believed that the adenine deficiency produced by orotic acid was caused by an inhibition of the reaction of PRPP with glutamine in the de novo purine synthesis, since large amounts of PRPP are utilized for the conversion of orotic acid to uridine-5 -phosphate. However, incorporation studies of glycine-1- C in livers of orotic acid-fed rats revealed that the inhibition is caused rather by a depletion of the PRPP available for reaction with glutamine than by an effect on the condensation itself [160]. 

The entry of calcium into neurons via presynaptic calcium channels is a key step in evoked neurotransmitter release. Compromised calcium channel function can lead to severe neurological consequences, and yet the pharmacological inhibition of specific calcium channel subtypes can be beneficial in the treatment of conditions such as neuropathic pain. Because of the importance of these channels, neurons have evolved complex means for regulating calcium channel activity, including activation of second messenger pathways by G protein coupled receptors and feedback inhibition by calcium binding proteins. By these means, neurons are able to maintain the fine balance of cytoplasmic calcium levels that is required for optimal neurotransmitter release. 

The cellular and molecular events involved in the dopamine-stimulated release of PTH can be clarified in experiments utilizing bovine parathyroid cells dispersed with collagenase and DNase (ft). This dispersion procedure yields parenchymal cells with only a slight contamination by red blood cells. The parenchymal cells exclude trypan blue and appear normal by light and electron microscopy (ft). These cells release PTH in a linear fashion for several hours the release is inhibited by calcium and stimulated by dopamine and beta-adrenergic agonists at concentrations comparable to those used to elicit physiological responses in vivo (ft,ft). 

Metarhodopsin II is inactivated by phosphorylation of three serine residues at the carboxyl terminal of the protein, catalyzed by rhodopsin kinase. In transgenic mice with carboxyl terminal-truncated rhodopsin, lacking the phosphorylation sites, there is a prolonged response to a single photon. Rhodopsin kinase is activated by its substrate, metarhodopsin II, and is inhibited by calcium bound to the protein recoverin, which thus prolongs the photoresponse. 

Calcium transport is essential for insulin secretion, which is therefore inhibited by calcium channel blockers (73). 

MGL activity in vitro is not affected by the addition of calcium to the incubation buffer (Sakurada and Noma 1981 Balsinde et al. 1991 Konrad et al. 1994). However, MGL activity could be inhibited by calcium, as two studies have reported an increase in activity following the addition of ethylene glycol-bis( -aminoethyl ether)N,N,N, N, -tetraacetic acid (EGTA) to the assay buffer (Sakurada and Noma 1981 Witting et al. 2004). Very high concentrations of sodium (i.e., 1 M) are inhibitory (Sakurada and Noma 1981) as is zinc (Tornqvist and Belfrage 1976). 

Shutov and Vaintraub [44] reported intensive deamidation activities of protein extracts from germinating seeds. Protein deamidases, prepared and purified from germinating wheat, kidney bean, and squash, were found to be specific to glutamine deamidation, not affected by reducing reagents, and partially inhibited by calcium ions [45]. Relative activity of these enzymes toward a variety of protein substrates were reported (Table 1) [46]. 

Husebye, E.S. Flatmark, T. Purification and kinetic properties of a soluble phosphatidylinositol-4-phosphate kinase of the bovine adrenal medulla with emphasis on its inhibition by calcium ions. Biochim. Biophys. Acta, 1010, 250-257 (1989)... 

Davis SD, lannetta A, Wedgwood RJ (1971) Activity of colistin against Pseudomonas aeruginosa inhibition by calcium. J Infect Dis 124(6) 610-612... 

COOKE, J. D. and QUASTEL, D. M. J. 1973. The specific effect of potassium on transmitter release by motor nerve terminals and its inhibition by calcium. J. Physiol. 228y 435-458. 

The feedback effects of the ion movements on the two enzymes, diesterase and cyclase, which are respectively responsible for the hydrolysis during the excitation and the synthesis of cGMP during the recovery, are of particular interest. The cyclase reaction is inhibited by calcium and cGMP synthesis is accelerated when the Ca " concentration is decreased by closure of the ion channels. The calcium cycle and relaxation is another interesting story. 

Hanski, E., Sevilla, N., and Levitzki, A., 1977, The allosteric inhibition by calcium of soluble and partially purified adenylate cyclase from turkey erythrocytes, Eur. J. Biochem. 76 513. 

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