Transport systems/transporters active

The first pharmacological agent shown to activate AMPK was 5-aminoimidazole-4-carboxamide (AICA) riboside, also known as acadesine. This adenosine analogue is taken up into cells by adenosine transporters and phosphoiylated by adenosine kinase to the mono-phosphorylated form, AICA ribotide or ZMP. ZMP accumulates inside cells to higher concentrations than the concentration of AICA riboside present in the medium, and it mimics both effects of AMP on AMPK system (allosteric activation and inhibition of... 

Neuromedin U is a neuropeptide which is widely distributed in the gut and central nervous system. Peripheral activities of neuromedin U include stimulation of smooth muscle, increase in blood pressure, alteration of ion transport in the gut, control of local blood flow and regulation of adrenocortical function. The actions of neuromedin U are mediated by G-protein coupled receptors (NMU1, NMU2) which are coupled tO Gq/11. 

Synaptic vesicles isolated from brain exhibit four distinct vesicular neurotransmitter transport activities one for monoamines, a second for acetylcholine, a third for the inhibitory neurotransmitters GABA and glycine, and a fourth for glutamate [1], Unlike Na+-dependent plasma membrane transporters, the vesicular activities couple to a proton electrochemical gradient (A. lh+) across the vesicle membrane generated by the vacuolar H+-ATPase ( vacuolar type proton translocating ATPase). Although all of the vesicular transport systems rely on ApH+, the relative dependence on the chemical and electrical components varies (Fig. 1). The... 

It is important to establish an in vitro system which will allow in vivo transport across the bile canalicular membrane to be predicted quantitatively. By comparing the transport activity between in vivo and in vitro situations in isolated bile canalicular membrane vesicles, it has been shown that there is a significant correlation for nine types of substrates [90]. Here, in vivo transport activity was defined as the biliary excretion rate, divided by the unbound hepatic concentration at steady-state, whereas in vitro transport activity was defined as the initial velocity for the transport into the isolated bile canalicular membrane vesicles divided by the medium concentration [90]. Collectively, it is possible to predict in vivo canalicular transport from in vitro experiments with the isolated bile canalicular membrane vesicles. 

BLM transport systems for ferrioxamine B were also devised based on first coordination shell recognition via ternary complex formation utilizing vacant coordination sites on the Fe(III) center (Fig. 29) (199). The tetra-coordinated substrate complex selectively transported was partially dechelated diaqua-ferrioxamine B and coordinately unsaturated di-hydroxamato iron(III) complexes, which utilized a hydrophobic membrane bound bidentate chelator as a carrier for selective transport. Active transport for these systems was accomplished using a pH gradient (199). 

Such complexation-reaction coupling processes may be of particular interest for the study of cation transport since they contain the possibility of devising systems undergoing active transport. 

Active transporters are thought to play an important role in the pharmacokinetics of drugs, not only because they can regulate the permeability of drugs as substrate-specific efflux or influx pumps, but also because of their widespread presence across in vivo membrane systems, from the intestinal epithelia to the BBB. Generally speaking, the absorption direction transporters tend to have narrower substrate specificity than the excretion direction transporters. Active transporters also play a significant role in biliary and renal excretion. 

The clinical relevance of data obtained from studies with single compounds is questionable, because most studies were performed in in vitro systems, limiting the predictability of the effects of the examined compounds in vivo. Moreover, some polyphenolics, such as quercetin, were shown to interact with the absorption or metabolism of drugs only at very high concentrations (50-100 pmol/L), which are likely to exceed the expected in vivo concentration after the consumption of a moderate amount of a grapefruit/ citrus product. Also, flavonoids have been demonstrated to potentially induce apoptosis in cell lines at concentrations comparable to those used for some in vitro drug interaction studies (64-66). This potentially could have impaired the investigation of enzyme and transporter activities. 

This must obviously be the opposite of passive transport. Active transport does require energy, usually in the form of the consumption of ATP or GTP, because the molecules are moving against the concentration gradient from an area of lower concentration to an area of higher concentration. The most well known active transport system is the Sodium-Potassium-ATPase Pump (Na" "- K+ZATPase) which maintains an imbalance of sodium and potassium ions inside and outside the membrane, respectively. See Figure 3. 

Some Systems of Active Transport Driven by ATP Hydrolysis... 

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