Transporters inhibition

Root, C., et al. Ileal bile acid transporter inhibition, CYP7A1 induction, and antilipemic action of 264W94. 

As a general rule, when two drugs are co-administered the compound with the higher potential to form H-bonds with the transporter inhibits or reverses the transport of the compound with the lower potential to form H-bonds, provided that the membrane concentration of compounds are comparable (e.g., Km). This phenomenon tends also to dominate drug-drug interactions related to P-gp, and is demonstrated in Figs. 20.11 and 20.13. 

It is seen that high para-selectivity should result from mass transport inhibition for formation of the undesirable m-/o-xylenes. 

A clear understanding of drug-binding sites and the mechanisms of transport/ inhibition as well as the resolution of P-gp crystal structures in complex with different substrates/inhibitors will definitively aid in the development of better models. However, considering the complexity underlying these antitargets, we strongly believe that this will not be reached in the near future. 

Cremaschi D, Porta C, Ghirardelli R (1996) The active transport of polypeptides in the rabbit nasal mucosa is supported by a specific vesicular transport inhibited by cytochalasin D. Biochim Biophys Acta 1283 101-105. 

Membrane transporters Inhibition of adenine nudeotide transporter by zidovudine... 

E-cadherin expression. Smoke extract, on pig airway epithelial cells and mouse trachea, produced a decrease of E-cadherin expression on membrane and an increase of cytoplasmic expression at 12 and 24 hours after exposure. The expression at 24 hours was higher than at 12 hours k Electron transport inhibition. Acetonitrile extracts of cigarette tar inhibited stage three and four respiration of intact mitochondria. Exposure of respiring submito-chondrial particles to the acetonitrile extracts of cigarette tar results in a dose-dependent inhibition of oxygen consumption... 

Chemicals can also interfere with the removal of the signal such as the level of a cation inside the cell. The signal is terminated by export of the cation through channels or transporters. Inhibition of these processes will prolong the signal and therefore the effect. Digitalis glycosides, which inhibit the Na+K+ ATPase so that Na+ levels rise in cardiac cells, is an example (see chap. 7). 

Mathesius U, Schlaman FIRM, Spaink PIP, Sautter C, Rolfe BG, Djordjevic MA. 1998. Auxin transport inhibition precedes root nodule formation in white clover roots and is regulated by flavonoids and derivatives of chitin oligosaccharides. Plant J 14 23-34. 

Amphetamine s primary effects (increased wakefulness, appetite suppression, and increased locomotor activity) are thought to be mediated by the release of norepinephrine from noradrenergic neurons in the CNS (36). However, research points to the role of plasma transport inhibition of dopamine, norepinephrine, and serotonin as well as inhibition of the vesicular monoamine transporter (138). Wisor et al. (139) summarize evidence that dopamine reuptake inhibition produces a greater alerting effect than norepinephrine transport blockade. 

Kaufman R, Rogers GA, Fehlmann C, Parsons SM (1989) Fractional vesamicol receptor occupancy and acetylcholine active transport inhibition in synaptic vesicles. Mol Pharmacol 36 452 158. 

Note A problem in the interpretation of the amiloride inhibition of proton release is the amiloride inhibition of di-ferric transferrin and ferricyanide reduction (Sun et al., 1987). The question arises does inhibition of the exchanger inhibit electron transport or does inhibition of electron transport inhibit a H release not dependent on the exchanger Exchanger inhibition is most likely because of the Na+ dependence for part of the H release (Sun et al., 1988). As an alternative, proton transport may be necessary for electron transport (Stahl and Anst, 1993). 

Yanase, D., Andoh, A., and Yasudomi, N. 1990. A new simple bioassay to evaluate photosynthesis electron-transport inhibition utilizing paraquat phytotoxicity. Pestic. Biochem. Physiol. 32, 92-98... 

An example of geometric isomerism is provided by the dimethylpyrrolidinecarboxanilides (18). Only when the methyl groups substituted on the pyrrolidine ring are in the ois-conformation is electron transport inhibited and phytotoxicity produced. The trans-isomer neither inhibits the Hill reaction, nor is it phytotoxic. 

A number of substances inhibit oxidative phosphorylation at specific locations. These may be divided into agents that affect electron transport, those that affect complex V, and those that collapse proton gradients (proton ionophores). Such substances have been used as research tools to unravel the complexities of these pathways, as poisons, and as antibiotics. Inhibition of electron transport inhibits phosphorylation, the extent of which depends on the location of the inhibition site. Thus, if complex I is inactivated, electron transport can still take place using FADH2 as an electron donor. The donor P/O ratio is then 2. 

Modifications are used to study different uptake transporters. Inhibition studies provide information about transporters involved in uptake. An alternative are cells overexpressing uptake transporters or oocyte studies with one expressed uptake transporter. 

V-Na+ CH (inactivated form) blocker (catecholamine transport inhibition) [central nervous system (CNS) stimulant, local anaesthetic, mydriatic, narcotic]... 

Olvanil (= A-(Vanillyl)-9-oleamide] (vanilloid phenolic) Cholecystokinin receptor Synthetic (cf. Capsaicin) Anandamide transport inhibition [14] (VR agonist) 5.8D... 

Polyoxometalates have found applications in analytical and clinical chemistry, catalysis (including photocatalysis), biochemistry (electron transport inhibition), medicine (antitumoral, antiviral, and even anti-HIV activity), and solid-state device [19,20], Recently, three-dimensional ordered materials are modified by the incorporation of POM into wall structures using a direct synthesis approach [21,22], The motivation for the work lies in the novel properties that POM is introduced into silica networks [19,20], The incorporation is that the POM is linked to silica matrix by covalent grafting. A class of POM that are particularly attractive for the preparation of hybrid materials are the lacunary POM. Lacunary POMs include the mono and divacant unsaturated Keggin fragments [X" W,039]< ">- (X"+=B Ge P [22], [ Y -SiWioOgg] [21], Lacunary... 

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