Calcium uptake system

PTH also acts to increase absorption of calcium ion by the small intestine. It does this indirectly by promoting the formation of active vitamin D in the kidney. PTH acts on the final, rate-limiting step in vitamin D synthesis, the formation of 1,25-dihydroxycholecalciferol in the kidney. If PTH is low, formation of the inactive derivative, 24,25-dihydroxycholecalciferol, is stimulated instead. Vitamin D acts on intracellular receptors in the small intestine to increase transcription of genes encoding calcium uptake systems, to up-regulate their expression. 

Histamine is stored within and released from neurons but a neuronal transporter for histamine has not been found. Newly synthesized neuronal histamine is transported into TM neuronal vesicles by the vesicular monoamine transporter VMAT2 [16]. Both in vivo and in vitro studies show that depolarization of nerve terminals activates the exocytotic release of histamine by a voltage- and calcium-dependent mechanism. Once released, histamine activates both postsynaptic and presynaptic receptors. Unlike the nerve terminals from other amine transmitters, however, histaminergic nerve terminals do not exhibit a high-affinity uptake system for histamine [5, 9, 23]. Astrocytes may contain a histamine transport system. 

As active transport uses a carrier system, it is normally specific for a particular substance or group of substances. Thus, the chemical structure of the compound and possibly even the spatial orientation are important. This type of transport is normally reserved for endogenous molecules such as amino acids, required nutrients, precursors, or analogues. For example, the anticancer drug 5-fluorouracil (Fig. 3.6), an analogue of uracil, is carried by the pyrimidine transport system. The toxic metal lead is actively absorbed from the gut via the calcium transport system. Active uptake of the toxic herbicide paraquat into the lung is a crucial part of its toxicity to that organ (see chap. 7). Polar and nonionized molecules as well as lipophilic molecules may be transported. As active transport may be saturated, it is a zero-order rate process in contrast to passive diffusion (Fig. 3.3). 

Calcium ions are bound with an identical high affinity of 5.106M by the purified ATPase, by the transport protein in the native membranes as well as by partially deli-pidated, reversibly inactivated membrane preparations"8, ll9 173). The amount of calcium which is bound with that high affinity corresponds to two sites per transport molecule. The observed affinity is in good agreement with the affinity derived from the dependence on ionized calcium of the activation of calcium uptake and ATP splitting as well as of the inhibition of calcium release and ATP synthesis18 u2,, 74 17s Since the latter experiments were performed under conditions which provide a constant internal free calcium concentration by the presence of oxalate or phosphate in the system, the reactions must have been activated or inhibited by the calcium ions... 

Glutamate is the primary excitatory neurotransmitter in the brain. Glutamate is formed by the Krebs cycle and is found free and stored in vesicles in synaptic terminals. Its release is calcium dependent, and an uptake system exists in presynaptic terminals and in glia to terminate its action after release. It is possible that glia metabolize glutamate to glutamine and return it to the neuron for reuse. An excessive release of glutamate can be lethal to cells in the immediate vicinity. 

These ion movements are shown schematically in Figure 11. It should be noted that the orientation of the protonmotive force is reversed from that in vivo. The proton-pumping Mg -ATPase will be described in a later section. This calcium transport system is not inhibited significantly by ruthenium red, the classical inhibitor for calcium uptake in mitochondria. However, uptake of Ca by these inside-out vesicles of E. coli is inhibited dramatically by a dimeric, mixed-valence complex of Ru" ", [(NH3)3RuCl3Ru(NH3)3]. The mode of action remains to be established. 

BHC produces a variety of neurological effects in insects and mammals. However, at both levels of the nervous system (peripheral and central), the mechanism of toxic action of BHC is poorly understood. Central nervous system stimulation appears to be due to blockade of the effects of y-aminobutyric acid. In vitro BHC isomers are reported to increase the calcium uptake of isolated rat brain synaptosomes. In addition, y-isomer of BHC has been shown to inhibit... 

The calcium-transport system is another potential source of binding proteins. Transport into mitochondria, across plasma membranes and through the intestinal mucosa and the renal tubule may be the function of distinct transport systems, each of which may be the source of binding proteins. The possibility of isolating bacterial mutants deficient both in calcium uptake and in calcium-binding proteins offers an interesting approach to the role of binding proteins in calcium transport. 

In order to establish a quantitative correlation between calcium transport and ATP splitting, i.e. the degree of coupling of the transport system, calcium uptake and calcium-dependent ATP splitting must be measured simultaneously. 

Although the precise role of taurine In retina Is not completely known there Is evidence that It can play an Inhibitory transmitter pole (16, 17) since It Is able to affect potassium and calcium fluxes at the Ionic membrane level (18-20), At the light of these findings It Is easily Interpreted the functional Inhibitory role of taurine In experiments In which from perfused chick and rat retina preloaded with 35S-taurlne light flashes enhance endogenous and labeled taurine release (21,22), Taurine Is the most potent amino acid able to reversibly abolish electroretinogram b wave (23-25) as well as to depress several neuronal populations from cerebral cortex, subcortical areas and spinal cord (26-29), In addition a specific uptake system has been described to occur In rat retina (30, 31) as well as In retinal pigment epithelium (32) and In slices and synaptosome preparations from various areas of the brain (33, 34),... 

The calcium rise in astrocyte B may cause multiple effects, including release of glutamate, via reversal of the uptake system. This may in turn modify the excitability of neuron C. 

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