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Iodide-Sulfate Exchanger
Shennan
Iodide transport in lactating rat mammary tissue via a pathway independent from the Na+/I- cotransporter: evidence for sulfate/iodide exchange.
Shennan DB.
Biochem Biophys Res Commun. 2001 Feb 9;280(5):1359-63.
"Although it is beyond doubt that mammary cells accumulate iodide via a Na+-dependent transport mechanism, it is not clear if this is the only pathway for iodide transport in mammary tissue. In view of this, experiments were designed to test for the presence of an anion-exchange pathway which could mediate the transport of iodide into mammary cells; thus, the effect of external iodide on sulfate efflux from rat mammary tissue has been investigated. Iodide trans-stimulated sulfate efflux from mammary tissue explants in a dose-dependent manner: 0.1, 1.0 and 10.0 mM iodide stimulated the fractional release of iodide by 56 +/- 2.2, 166.5 +/- 17.5, and 302.9 +/- 29.8%, respectively. The stimulation of sulfate efflux by external iodide was completely inhibited by DIDS (4.4'-diisothiocyanatostilbene 2,2'-disulfonic acid). Perchlorate (1 mM) also trans-stimulated sulfate efflux in a manner that was inhibited by DIDS. Furthermore, iodide trans-accelerated sulfate efflux from rat mammary acini via a DIDS-sensitive mechanism. The results are consistent with the presence of a DIDS-sensitive anion-exchange mechanism which can accept iodide as a substrate. It appears that the iodide-sulfate exchange mechanism is independent from the sodium-dependent iodide transporter given that sulfate is not a substrate of the latter system. The iodide-sulfate exchanger may operate in parallel with the sodium-dependent iodide transporter to mediate iodide uptake into mammary cells."
Transport of milk constituents by the mammary gland.
Shennan DB, Peaker M.
Physiol Rev. 2000 Jul;80(3):925-51. Review.
"This review deals with the cellular mechanisms that transport milk constituents or the precursors of milk constituents into, out of, and across the mammary secretory cell. The various milk constituents are secreted by different intracellular routes, and these are outlined, including the paracellular pathway between interstitial fluid and milk that is present in some physiological states and in some species throughout lactation. Also considered are the in vivo and in vitro methods used to study mammary transport and secretory mechanisms. The main part of the review addresses the mechanisms responsible for uptake across the basolateral cell membrane and, in some cases, for transport into the Golgi apparatus and for movement across the apical membrane of sodium, potassium, chloride, water, phosphate, calcium, citrate, iodide, choline, carnitine, glucose, amino acids and peptides, and fatty acids. Recent work on the control of these processes, by volume-sensitive mechanisms for example, is emphasized. The review points out where future work is needed to gain an overall view of milk secretion, for example, in marsupials where milk composition changes markedly during development of the young, and particularly on the intracellular coordination of the transport processes that result in the production of milk of relatively constant composition at a particular stage of lactation in both placental and marsupial mammals."
Substrate specificity of the mammary tissue anionic amino acid carrier operating in the cotransport and exchange modes.
Millar ID, Calvert DT, Lomax MA, Shennan DB.
Biochim Biophys Acta. 1997 May 22;1326(1):92-102. Erratum in: Biochim Biophys Acta 1997 Dec 4;1330(2):293.
[abstract only]
"The substrate specificity of the rat mammary tissue high affinity, Na+-dependent anionic amino acid transport system has been investigated using explants and the perfused mammary gland. D-Aspartate appears to be transported via the high affinity, Na+-dependent L-glutamate carrier. Thus, D-aspartate transport by rat mammary tissue was Na+-dependent and saturable with respect to extracellular D-aspartate with a Km and Vmax of 32.4 microM and 49.0 nmol/2 min per g of cells respectively. The uptake of D-aspartate by mammary explants was cis-inhibited by L-glutamate and L-aspartate, but not by D-glutamate. L-glutamate uptake by mammary tissue explants was cis-inhibited by beta-glutamate, L-cysteate, L-cysteine sulfinate and dihydrokainate but not by DL-alpha-aminoadipate. In addition, dihydrokainate, but not DL-alpha-aminoadipate inhibited D-aspartate and L-glutamate uptake by the perfused gland. D-Aspartate efflux from mammary tissue explants was trans-accelerated by external L-glutamate in a dose-dependent fashion (50-500 microM). The effect of L-glutamate on D-aspartate efflux was dependent on the presence of extracellular Na+. D-Aspartate, L-aspartate and L-cysteine sulfinate (at 500 microM) also markedly trans-stimulated D-aspartate efflux from mammary tissue explants. In contrast, L-cysteine. D-glutamate, L-leucine, dihydrokainate and DL-alpha-aminoadipate were either weak stimulators of D-aspartate efflux or were without effect. D-Aspartate efflux from the perfused mammary gland was trans-stimulated by L-glutamate but not by D-glutamate and only weakly by L-cysteine (all at 500 microM). It appears that the mammary tissue high affinity anionic amino acid carrier can operate in the exchange mode with a similar substrate specificity to that of the co-transport mode."
The effect of a hyposmotic shock on amino acid efflux from lactating rat mammary tissue: stimulation of taurine and glycine efflux via a pathway distinct from anion exchange and volume-activated anion channels.
Shennan DB, McNeillie SA, Curran DE.
Exp Physiol. 1994 Sep;79(5):797-808.
"We have examined the effect of a hyposmotic shock, and thus cell swelling, upon the efflux of amino acids, SO4(2-) and I- from lactating mammary tissue. A hyposmotic challenge increased the efflux of taurine and glycine via a 4,4'-diisothiocyanatostilbene-2,2'- disulphonic acid (DIDS)-sensitive pathway. It appears that these amino acids do not exit via an anion-exchange mechanism following cell swelling because sulphate efflux, which uses a DIDS-sensitive exchange mechanism, was unaffected. The hyposmotic-induced efflux of taurine was not dependent upon the Na+ gradient and was not influenced by the nature of the anion in the incubation medium. In addition, taurine efflux was stimulated by incubating mammary tissue in an isosmotic medium that contained urea, suggesting that cell swelling is the stimulating factor rather than a decrease in osmolality per se. The results suggest that mammary tissue uses taurine and glycine as a means of regulating cell volume following swelling. In contrast, the efflux of glutamic acid, alanine and alpha-aminoisobutyric acid was unaffected by a hyposmotic challenge. Similarly, the efflux of I- was unaffected by such a challenge. The results suggest that volume-activated amino acid transport in lactating rat mammary tissue is distinct from volume-regulated anion channels."
A study of sulphate transport by lactating rat mammary tissue slices: evidence for anion exchange.
Shennan DB.
Comp Biochem Physiol A. 1989;92(1):145-50.
[abstract only]
"1. The efflux of radiolabelled sulphate from lactating rat mammary tissue slices has been studied. Sulphate efflux was found to be time- and temperature-dependent.
2. 4,4'-Diisothiocyanostilbene-2,2'-disulphonate (DIDS) inhibited a portion of sulphate release, whereas bumetanide was without effect.
3. The anions chloride, iodide and sulphate trans-stimulated sulphate efflux when added to the incubation medium. The increase in the efflux rate of sulphate found with chloride could be markedly inhibited by DIDS. Thiocyanate, unlike the other anions tested, only had a small effect.
4. The results strongly suggest that there is an anion exchange mechanism in the mammary gland which can mediate the transport of sulphate. This transporter may be important for the metabolism of sulphate by the mammary gland and may also help determine milk anion concentrations."