Countertransport

Fig. 5. A schematic mechanism for the carrier mediated countertransport of a metal ion and a proton. (Cited from Ref. 29>)...

Additional cellular events linked to the activity of blood pressure regulating substances involve membrane sodium transport mechanisms Na+/K.+ ATPase Na+fLi countertransport Na+ -H exchange Na+-Ca2+ exchange Na+-K+ 2C1 transport passive Na+ transport potassium channels cell volume and intracellular pH changes and calcium channels. 

Figure 10 Schematic of cotransporters and countertransporters (or exchangers) in en-terocyte mucosal and basolateral membranes.

Both secondary active transport and positive cooperativity effects enhance carrier-mediated solute flux, in contrast to negative cooperativity and inhibition phenomena, which depress this flux. Most secondary active transport in intestinal epithelia is driven by transmembrane ion gradients in which an inorganic cation is cotransported with the solute (usually a nutrient or inorganic anion). Carriers which translocate more than one solute species in the same direction across the membrane are referred to as cotransporters. Carriers which translocate different solutes in opposite directions across the membrane are called countertransporters or exchangers (Figs. 10 and 11). 

Differences in the Na+-Li+ countertransport process have also been observed in the erythrocytes of psychiatric patients [67]. Pandey reported that this process was generally slower in bipolar patients than in normal controls, leading to the observed higher Li+ ratios, although many patients still had Li+ ratios in the normal range [68]. 

A decrease in the efficiency of the Na+-Li+ countertransport is also observed as a direct result of Li+ administration, with a 50% inhibition in the efflux of Li+ from the erythrocytes of people on Li+ therapy [63], This decrease in activity occurs 2-4 days after commencing therapy and maximum reduction appears within 7 days the rate of transport returns to normal soon after the Li+ administration is ceased. This Li+-induced change has been attributed to a decrease in the affinity of the transporter for Li+ as the /sTmfor the process increases threefold, whereas Vmaxremains constant, in contrast to the interindividual variability [69]. 

Fig. 2. Schematic diagram of the stoichometry of ion flux coupling and the chloride channel activity of glutamate transporters. Glutamate is coupled to the co-transport of 3 Na+, 1K+, and the countertransport of 1 K+. In addition, glutamate and Na+ binding to the transporter activates an uncoupled chloride flux through the transporter.

These methods of solute transfer usually rely on a relatively low intracellular concentration of the solute of interest, so that it will readily diffuse into the cell down the electrochemical gradient (as in the case of ion channels). Alternatively, the solute may be moved into the cell using chemical energy derived from another solute moved in the same direction (co-transport) or opposite direction (countertransport) on the carrier protein (symporters and antiporters respectively). The transfer of the second solute is in turn dependent on an inward electrochemical gradient. Ultimately, these gradients are established by primary, energy-requiring solute pumps (e.g. ATPases), which, on most epithelia, are located on the basolateral/serosal membrane (see Section 5.2 for discussion of ATPases). 

Ehrensing RH, Kastin AJ Dose-related biphasic effect of prolyl-leucylglycinamide (MlF-1) in depression. Am J Psychiatry 135 562-566, 1978 Ehrlich BE, Diamond JM, Ery V, et al Lithium s inhibition of erythrocyte cation countertransport involves a slow process in the erythrocyte. J Membr Biol 75 233-240, 1983... 

Figure 33. Principle of proton-driven uphill transport for dopamine under a countertransport mode. The concentration of the carrier lasalocid A in o-dichlorobenzene was 0.1 M. The feed phase (100 ml) was 10 mM Tris-HCI buffer solution (pH 7.4) containing 1 mM ascorbic acid. The receiving phase (0.5-2.0 ml) was a hydrochloric acid solution (pH 0.5-3.0). The initial dopamine concentration in the feed solution was in the range from 1.00 x 10 to 1.00 x 10 M (reprinted with permission from Anal. Sci. 1996, 12, 333. Copyright 1996 The Japan Society for Analytical Chemistry).

Schork NJ, Gardner JP, Zhang L et al. Genomic association/linkage of sodium lithium countertransport in CEPH pedigrees. Hypertension 2002 40 619-628. 

To minimize the variability of exposure to Rapamune, this drug should be taken consistently with or without food. Grapefruit juice reduces CYP3A4-mediated drug metabolism and potentially enhances P-gp-mediated drug countertransport from enterocytes of the small intestine. This juice must not be administered with Rapamune or used for dilution... 

Systematically speaking, so-called internal oxidation reactions of alloys (A,B) are extreme cases of morphological instabilities in oxidation. Internal oxidation occurs if oxygen dissolves in the alloy crystal and the (diffusional) transport of atomic oxygen from the gas/crystal surface into the interior of the alloy is faster than the countertransport of the base metal component (B) from the interior towards the surface. In this case, the oxidation product BO does not form a stable oxide layer on the alloy surface. Rather, BO is internally precipitated in the form of small oxide particles. The internal reaction front moves parabolically ( Vo into the alloy. Examples of internal reactions are discussed quantitatively in Chapter 9. 

Further demonstrations of this sort of counterflow phenomenon for many different substrates in virtually every type of cell have been used as functional hallmarks of carrier-mediated transport. Experimental demonstration of this effect precludes transport being mediated either by simple diffusion or by fixed pores in the membrane. In reviewing 20 years of experimental work related to the carrier hypothesis, LeFevre (1975) lists a number of key functional properties of carrier mediated transport, all of which have stood the test of the subsequent 20 years. These include saturation of transport with increased substrate concentration and associated phenomena such as competition between similar substrates, high rates of unidirectional transport, and countertransport. Also covered are flux coupling (including trans effects and cotransport), chemical specificity, inhibition by protein-specific reagents, hormonal regulation, and a steep dependence of the rate of transport on temperature (included only to bemoan its common inclusion in textbooks ). 

FIGURE 4.6 Illustration of the SLM-coupled countertransport of an anionic herbicide (glyphosate) metabo lite, AMPA- (left) and a cationic metal ion, M+ (right). 

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