Calcium, competitive inhibition

PCP also increases calcium-independent [3H]DA release from dissociated rat mesencephalon cell cultures122 and striatal synaptosomes.123 PCP has been found to be a potent inhibitor of [3H]DA uptake in rat striatum,124 127 to competitively inhibit binding of [3H]BTCP, a PCP derivative and... 

Kober, T.E. and G.P Cooper. 1976. Lead competitively inhibits calcium-dependent synoptic transmission in the bullfrog sympathetic ganglion. Nature (Lond). 262 704-705. 

Antagonist X (competitive) has an affinity for Rb but not Ra. Thus, it specifically antagonizes agonist B. It does not antagonize agonist A. Antagonist Y acts on a receptor associated with the cellular translocation of calcium and inhibits the increase in intracellular free calcium. It will therefore antagonize the effects of both A and B, since they both ultimately depend on calcium movement to cause contraction. 

In conclusion, research results indicate that calcium apparently inhibits the absorption of manganese from the intestinal tract. Different sources of calcium apparently affect manganese to varying degrees. Whether or not this is due to changes in intestinal acidity/alkalinity, to possible competition between manganese and calcium for absorption sites, or to a combination of factors is unknown. 

Probably, the intrinsic calcium is important for maintaining the protein in an active conformation (about 5 calcium atoms are present per molecule molecular weight, 750,000 calculated for 275 y of calcium/g. of enzyme), and extraneously added calcium is bound near the active site, thus blocking it, or reacts with one of the groups on the active site. The inhibition is instantaneous and of non-< ompetitive character, with an inhibitor constant (Ki) of 5.3 X 10 M at 20° and pH 7.6 (compare the non-competitive inhibition by beryllium with Ki = 2.9 X 10 Af under the same conditions). 

Foscarnet competitively inhibits Na -Pj cotransport in animal and human kidney proximal tubule brush border membrane vesicles, reversibly inhibiting sodium-dependent phosphate transport [48, 49]. Renal cortical Na-K-ATPase and alkaline phosphatase activity are not inhibited by foscarnet, nor is proline, glucose, succinate, or Na" transport [48,49]. Foscarnet induces isolated phosphaturia without hypophosphatemia in thyroparathyroidectomized rats maintained on a low phosphorus diet, without affecting glomerular filtration rate, urinary adenosine 3 5 -cyclic monophosphate (cAMP) activity, or urinary calcium, sodium or potassium excretion [48,50]. Sodium-Pj cotransport in brush border membrane vesicles from human renal cortex was reported to be even more sensitive to inhibition by foscarnet than in rat renal brush border membrane vesicles [49]. 

Calcium binding was assayed by ultrafiltration and was found to exhibit a />H optimum at about 7.4. One class of binding sites is present which bind one mole of calcium per mole of protein with a dissociation constant equal to 2.5 X 10 5M. Calcium binding was competitively inhibited by other divalent cations the binding affinity being Ca++, Mn++, Sr++, Ba++, Mg++ (160). Lanthanum salts irreversibly precipitate brain CBP-II. Those cations which are the most effective inhibitors of calcium binding to this protein are also the most active for in vitro calcium-dependent release of neurotransmitters. 

Calcium (>50yM) inhibits basal, hormone-stimulated. GppNHp stimulated, and forskolin stimulated adenylate cyclase. 3 This inhibition is not competitive with forskolin and has been suggested to be due to the interaction of the metal ion at a cation binding site on the catalytic subunit. 

Nishimura M. 1987. Zinc competitively inhibits calcium-dependent release of transmitter at the mouse neuromuscular junction. Pfiugers Archiv 410 623-626. 

The mechanism of action of the 35-kDa CKBP is competitive inhibition of CC-chemokine binding to cellular receptors, inhibiting as a consequence the induction of transient increases in calcium concentrations and the migration of cells aloi chemotactic gtadients. - The M-Tl protein of MYXV has the unique ability to interact with GAGs via a GAG bindii domain at its C-terminus that is not present in other 35-kDa fiunily members. This unique property of M-Tl would retain the protein in the vicinity of infected cells and may enhance its abUity to protect the sites of infection from chemoldne-mediated anti-viral responses. 

Lead has been shown to inhibit calcium competitively in a variety of biological systems, e.g. in the superior cervical ganglion of the cat (Kostial and Vouk, 1957) in presynaptic terminals in frog sympathetic ganglion (Kober and Cooper, 1977) in adrenergic synapses in the rabbit saphenous... 

Cadmium accumulation by MDCK cells also appears to be mediated in part by agonist-stimulated calcium channels (Flanagan and Friedman 1991). Parathyroid hormone, a stimulator of calcium uptake in MDCK cells, increased cadmium uptake. The dihydropyridine agonist BAY K8644 augmented the effect of parathyroid hormone, an effect that was competitively inhibited by the calcium channel antagonist nifedipine (Flanagan and Friedman 1991). 

Molybdenum contained in food is resorbed in aU parts of the small intestine and in part previously in the stomach. Resorption is quite effective (25-80%). With the exception of Mo 2, molybdenum is resorbed well from the soluble compounds (such as sodium and ammonium molybdates) and less soluble compounds (molybdenum trioxide and calcium molybdate). Resorption of molybdenum is competitively inhibited by sulfate anions. The excess of molybdenum is excreted in the urine. 

Kober, T. E. and Cooper, G. P. (1976). Lead competitively inhibits calcium dependent synaptic transmission in the bullfixjg S3mipathetic ganglion. Nature 262, 704-705. 

Diazoxide - An Jji vitro pharmacodynamic study was de-signed to specify the type(s) of inhibition involved in the vascular action of diazoxide. The results indicate that diaz> oxide competes with barium for a specific receptor site in the vascular smooth muscle of the rat aorta. The location of this receptor is apparently closer to the process of muscle contraction than the a-adrenergic receptor, and may be a site normally activated by calcium. The specific competitive inhibition of barium-stimulated vasoconstriction by diazoxide may help to explain the mechanism by which diazoxide, and possibly other benzothiadiazine antihypertensive agents, reduce blood pressure. ... 

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