Uptake activation

After release there must be some way of terminating the action of a NT necessitating the presence of an appropriate enzyme and/or uptake mechanism. Such uptake processes can be quite specific chemically. Thus a high-affinity uptake (activated by low concentrations) can be found for glycine in the cord where it is believed to be a NT, but not in the cortex where is has no such action. This specific uptake can be utilised to map terminals for a particular NT, especially if it can be labelled, and also for loading nerves with labelled NT for release studies. 

Feedback inhibition of amino acid transporters by amino acids synthesized by the cells might be responsible for the well known fact that blocking protein synthesis by cycloheximide in Saccharomyces cerevisiae inhibits the uptake of most amino acids [56]. Indeed, under these conditions, endogenous amino acids continue to accumulate. This situation, which precludes studying amino acid transport in yeast in the presence of inhibitors of protein synthesis, is very different from that observed in bacteria, where amino acid uptake is commonly measured in the presence of chloramphenicol in order to isolate the uptake process from further metabolism of accumulated substances. In yeast, when nitrogen starvation rather than cycloheximide is used to block protein synthesis, this leads to very high uptake activity. This fact supports the feedback inhibition interpretation of the observed cycloheximide effect. 

Varanasi U, JE Stein, M Nishimoto, WL Reichert, TK Collier (1987) Chemical carcinogenesis in feral fish uptake, activation, and detoxication of organic xenobiotics. Environ Health Perspect 71 155-170. 

Militante JD, Lombardini JB (1999) Taurine uptake activity in the rat retina protein kinase C-independent inhibition by chelerythrine. Brain Res 818 368-374... 

Taylor, R.S., Jones, S.M., Dahl, R.H., Nordeen, M.H., and Howell, K.E., 1997, Characterization of the Golgi complex cleared of proteins in transit and examination of calcium uptake activities. Mol. Biol. Cell 8, 1911-1931... 

Passive diffusion, carrier-mediated uptake, active uptake, filtration in elimination organs... 

In other recent reports concerning enzymatic inhibition and receptor binding of organofullerene materials, C60 monomalonate adducts were found to selectively inactivate the neuronal nitric oxide synthase isoform in a manner completely preventable by the concurrent presence of superoxide dismutase and catalase [295]. Also two fullerene-steroid hybrids were synthesized and found to decrease both the ATP hydrolysis and Ca2+ uptake activity of SR Ca2+-ATPase while the inhibitions were concentration dependent [296]. 

A relatively simple and quick procedure for the isolation of Photosystem I-enriched particles from the thermophilic cyanobacterium Phormidium laminosum, without the use of detergents for solubilization, is described. The procedure involves sonication of cells, centrifugation and DEAE-cellulose chromatography. The particles had an 02 uptake activity of up to 200 pmol 02. mg chlorophyll h 1 and appeared as vesicles of 200 100 nm diameter when observed under electron microscopy. The analysis of the chlorophyll-protein complexes by polyacrylamide gel electrophoresis showed that these particles are enriched in the complexes associated with Photosystem I and partially depleted in those associated with Photosystem II. The particles did not contain ferredoxin and were active in NADP-photoreduction only in the presence of added ferredox in. They were also able to photoreduce externally added electron mediators using ascorbate as electron donor, the reduced mediators can be coupled to hydrogenase for the production of H2 or for the activation of cyanobacterial phosphoribulokinase using a ferredoxin/thioredoxin system. 

Glibenclamide Synthetic activation phos n, IRS-1 phos n, PI3K, PKB Glc uptake activation] ATP-K+ CH [1 nM] (CFTR)... 

A number of factors must be considered in the area of stereoselectivity (31). Distinct differences are noted between stereoisomers in absorption/ uptake, activity at the target or receptor site, pathways and rate of bioconversion, and pharmacokinetics. All of these factors are applicable in the case of triadimefon and are examples of processes that may be manipulated to enhance disease control effectiveness. 

Guan, L. L., Kanoh, K., and Kamino, K. (2001). Effect of exogenous siderophores on iron uptake activity of marine bacteria under iron-limited conditions. Appl. Environ. Microbiol. 67, 1710-1717. 

Hansch and Caldwell have analyzed the quantitative structure/activity relationships (QSAR) of a series of amphetamine and 2-phenethylamine analogs, to discern the role of steric and hydrophobic aryl substituents on the inhibition of 5-HT uptake (142). From the biological data of 19 compounds, including those in Table 15.13. and some additional analogs, the following equation was derived for inhibition of uptake activity, where C is the IC concentration, MR4 is the molar refrac-tivity value of the aryl substituent scaled by 0.1, and 7T3 is the hydrophobicity of the meUi substituent on the aryl ring ... 

The SAR for norepinephrine uptake inhibition by amphetamine analogs is similar to that for inhibition of 5-HT reuptake. The protypical unsubstituted derivative, 2-phenethyl-amine, is a weak uptake inhibitor in isolated rat heart membranes (IDgo = 1.1 jM) (143). Introduction of a methyl group at the Cl position adjacent to the amino group results in a 10-fold increase in potency (i.e., dexamphetamine, (8), 1D = 0.18 pAO (143). Sibutra-mine, a tertiary amine, shows moderate NE uptake activity iK = 350 nAO, but its des-methyl and di-desmethyl metabolites, (JD-BTS 54 354 (44) and (R)-BTS 54 505 (46), exhibit potent activity values <20 nM) (see Table 15.10) (71). 

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