Comparison of Lactate Transport in Astroglial Cells and Monocarboxylate Transporter 1 (MCT 1) Expressing Xenopus laevis Oocytes

The transport of lactate is an essential part of the concept of metabolic coupling between neurons and glia. Lactate transport in primary cultures of astroglial cells was shown to be mediated by a single saturable transport system with aK m value for lactate of 7.7 mm and aV max value of 250 nmol/(min × mg of protein). Transport was inhibited by a variety of monocarboxylates and by compounds known to inhibit monocarboxylate transport in other cell types, such as α-cyano-4-hydroxycinnamate andp-chloromercurbenzenesulfonate. Using reverse transcriptase-polymerase chain reaction and Northern blotting, the presence of mRNA coding for the monocarboxylate transporter 1 (MCT1) was demonstrated in primary cultures of astroglial cells. In contrast, neuron-rich primary cultures were found to contain the mRNA coding for the monocarboxylate transporter 2 (MCT2). MCT1 was cloned and expressed in Xenopus laevis oocytes. Comparison of lactate transport in MCT1 expressing oocytes with lactate transport in glial cells revealed that MCT1 can account for all characteristics of lactate transport in glial cells. These data provide further molecular support for the existence of a lactate shuttle between astrocytes and neurons. The transport of lactate is an essential part of the concept of metabolic coupling between neurons and glia. Lactate transport in primary cultures of astroglial cells was shown to be mediated by a single saturable transport system with aK m value for lactate of 7.7 mm and aV max value of 250 nmol/(min × mg of protein). Transport was inhibited by a variety of monocarboxylates and by compounds known to inhibit monocarboxylate transport in other cell types, such as α-cyano-4-hydroxycinnamate andp-chloromercurbenzenesulfonate. Using reverse transcriptase-polymerase chain reaction and Northern blotting, the presence of mRNA coding for the monocarboxylate transporter 1 (MCT1) was demonstrated in primary cultures of astroglial cells. In contrast, neuron-rich primary cultures were found to contain the mRNA coding for the monocarboxylate transporter 2 (MCT2). MCT1 was cloned and expressed in Xenopus laevis oocytes. Comparison of lactate transport in MCT1 expressing oocytes with lactate transport in glial cells revealed that MCT1 can account for all characteristics of lactate transport in glial cells. These data provide further molecular support for the existence of a lactate shuttle between astrocytes and neurons. The transport of lactate is an essential part of the concept of metabolic coupling between neurons and glia (1Dringen R. Wiesinger H. Hamprecht B. Neurosci. Lett. 1993; 163: 5-7Crossref PubMed Scopus (108) Google Scholar, 2Tsacopoulos M. Magistretti P.J. J. Neurosci. 1996; 16: 877-885Crossref PubMed Google Scholar). It has been demonstrated that glutamate at concentrations around 200 μm strongly increases the rates of glycolysis and lactate release in cultured astroglial cells (3Pellerin L. Magistretti P.J. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 10625-10629Crossref PubMed Scopus (2182) Google Scholar). It has further been shown that neurons are able to take up lactate and to use this compound as an energy substrate (1Dringen R. Wiesinger H. Hamprecht B. Neurosci. Lett. 1993; 163: 5-7Crossref PubMed Scopus (108) Google Scholar, 4Schurr A. Rigor B.M. Science. 1988; 240: 1326-1328Crossref PubMed Scopus (484) Google Scholar, 5Schneider U. Poole R.C. Halestrap A.P. Grafe P. Neuroscience. 1993; 53: 1153-1162Crossref PubMed Scopus (23) Google Scholar). In the mammalian retina, direct evidence has been provided for a transfer of lactate between Müller glial cells and photoreceptors (6Poitry-Yamate C.L. Poitry S. Tsacopoulos M. J. Neurosci. 1995; 15: 5179-5191Crossref PubMed Google Scholar). Besides its role as an exchangeable metabolic fuel, lactate also interferes with pH and volume regulation in neural cells (7Siesjö B.K. Neurochem. Pathol. 1988; 9: 31-88PubMed Google Scholar). There is a considerable debate over the types of transporters involved in the uptake and release of lactate by astroglial cells. Nedergaard and Goldman (8Nedergaard M. Goldman S.A. Am. J. Physiol. 1993; 265: R282-R289PubMed Google Scholar) characterized lactate transport in cultured astrocytes and determined a low K m value of 0.4 mm. The carrier-mediated transport could not be inhibited by α-cyano-3-hydroxycinnamate or pCMBS, 1The abbreviations used are: pCMBS,p-chloromercuribenzenesulfonate; HBSS, Hank's buffered salt solution; MCT, monocarboxylate transporter; bp, base pair(s). both being typical inhibitors of monocarboxylate transport in other cell types. The transport process was reversible and accompanied by a cotransport of protons. Diffusion of protonated lactate could not be detected. In contrast to these results, Tildon et al. (9Tildon J.T. McKenna M.C. Stevenson J. Couto R. Neurochem. Res. 1993; 18: 177-184Crossref PubMed Scopus (90) Google Scholar) identified two carrier-mediated processes for lactate uptake, characterized byK m values of 0.5 mm and 11 mm, respectively. The maximum velocity of the low-affinity transporter was 170 nmol/(min × mg of protein), whereas only 10% of this value was found for the high affinity component. Transport was only partially inhibited by α-cyano-4-hydroxycinnamate and mersalyl. Acidic pH strongly increased transport activity, a finding consistent with a lactate/proton cotransport mechanism. Dringen et al.(10Dringen R. Peters H. Wiesinger H. Hamprecht B. Dev. Neurosci. 1995; 17: 63-69Crossref PubMed Scopus (47) Google Scholar) detected solely non-saturable lactate transport in primary cultures of astroglial cells which could not be inhibited by α-cyano-3-hydroxycinnamate or α-cyano-4-hydroxycinnamate and strongly increased when the pH value was lowered. Volk et al. (11Volk C. Kempski B. Kempski O. Neurosci. Lett. 1997; 223: 121-124Crossref PubMed Scopus (37) Google Scholar) showed that lactate release from astroglial cells could be inhibited by quercetin but not by α-cyano-4-hydroxycinnamate. Recently three different cDNAs were identified which encode H+/monocarboxylate cotransporters of mammalian cells (12Kim C.M. Goldstein J.L. Brown M.S. J. Biol. Chem. 1992; 267: 23113-23121Abstract Full Text PDF PubMed Google Scholar, 13Kim-Garcia C. Goldstein J.L. Pathak R.K. Anderson R.G.W. Brown M.S. Cell. 1994; 76: 865-873Abstract Full Text PDF PubMed Scopus (481) Google Scholar, 14Garcia C.K. Brown M.S. Pathak R.K. Goldstein J.L. J. Biol. Chem. 1995; 270: 1843-1849Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar, 15Yoon H. Fanelli A. Grollmann E.F. Philp N.J. Biochem. Biophys. Res. Commun. 1997; 234: 90-94Crossref PubMed Scopus (128) Google Scholar, 16Takanaga H. Tamai I. Inaba S. Sai Y. Higashida H. Yamamoto H. Tsuji A. Biochem. Biophys. Res. Commun. 1995; 217: 370-377Crossref PubMed Scopus (103) Google Scholar) and were designated MCT1, MCT2, and MCT3. MCT1 is expressed in erythrocytes, lung, heart, skeletal muscle, and the basolateral membranes of the intestinal epithelium; MCT2 predominates in heart, liver, kidney, and testis. MCT3 was isolated from retinal pigment epithelium, its tissue distribution has not been established. Contrasting results have been reported concerning expression in the brain; thus neither MCT1 nor MCT2 were detected in brain in two studies (12Kim C.M. Goldstein J.L. Brown M.S. J. Biol. Chem. 1992; 267: 23113-23121Abstract Full Text PDF PubMed Google Scholar, 14Garcia C.K. Brown M.S. Pathak R.K. Goldstein J.L. J. Biol. Chem. 1995; 270: 1843-1849Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar), whereas MCT1 mRNA was detected in rat brain in two other studies. (16Takanaga H. Tamai I. Inaba S. Sai Y. Higashida H. Yamamoto H. Tsuji A. Biochem. Biophys. Res. Commun. 1995; 217: 370-377Crossref PubMed Scopus (103) Google Scholar, 17Jackson V.N. Price N.T. Carpenter L. Halestrap A.P. Biochem. J. 1997; 324: 447-453Crossref PubMed Scopus (127) Google Scholar). The physiological properties of MCT1 have been investigated extensively (18Carpenter L. Halestrap A.P. Biochem. J. 1994; 304: 751-760Crossref PubMed Scopus (121) Google Scholar, 19Deuticke B. J. Membr. Biol. 1982; 70: 89-103Crossref PubMed Scopus (149) Google Scholar). Transport of pyruvate by MCT2 has been investigated in transfected cells (14Garcia C.K. Brown M.S. Pathak R.K. Goldstein J.L. J. Biol. Chem. 1995; 270: 1843-1849Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar). The well characterized lactate transport in liver cells (20Jackson V.N. Halestrap A.P. J. Biol. Chem. 1996; 271: 861-868Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar) might reflect the action of both MCT1 and MCT2 (17Jackson V.N. Price N.T. Carpenter L. Halestrap A.P. Biochem. J. 1997; 324: 447-453Crossref PubMed Scopus (127) Google Scholar). In this report we present functional and molecular evidence that MCT1 is the only monocarboxylate transporter of astroglial cells, whereas cultured neurons express the transporter isoform MCT2. High level expression of MCT1 in Xenopus laevis oocytes allowed the investigation of transport properties of MCT1 using 14Clactate as a substrate. The transport properties of MCT1 expressed in oocytes are in agreement with transport data gained with astroglia-rich primary cultures. Radiochemicals were purchased from Amersham Buchler (Braunschweig, Germany) or from DuPont (Regensdorf, Switzerland). Fetal calf serum was supplied by Boehringer (Mannheim, Germany) or Fakola AG (Basel, Switzerland). Superscript reverse transcriptase was from Life Technologies, Eggenstein (Germany) and Dulbecco's modified Eagle's medium was obtained from Life Technologies or Sigma (Buchs, Switzerland). The Cap-analogue m7G(5′)ppp(5′)G was purchased from New England Biolabs, Schwalbach (Germany). GeneScreen membranes were obtained from Life Science Products, Regensdorf (Switzerland), RNasin from Promega, Mannheim (Germany), and Ultima Gold scintillation mixture from Canberra Packard, Frankfurt (Germany). All other chemicals were of analytical grade and supplied by E. Merck, Darmstadt, Germany; Roth, Karlsruhe, Germany; Boehringer, Mannheim, Germany; or Sigma, Buchs, Switzerland; or Deisenhofen, Germany. Astroglia-rich primary cultures were prepared from brains of neonatal Wistar rats and cultured as described by Hamprecht and Löffler (21Hamprecht B. Löffler F. Meth. Enzymol. 1985; 109: 341-345Crossref PubMed Scopus (238) Google Scholar). Primary cultures of mouse cerebral astrocytes were prepared from as described by and Magistretti O. Magistretti P.J. Res. PubMed Scopus Google Scholar). neurons of glial cells were prepared as described L. Magistretti P.J. J. Neurosci. 1995; 15: PubMed Google Scholar). uptake rat astroglial cells were to a of × in a of 10% in at in Dulbecco's modified Eagle's 10% calf serum mm All were at medium was and cells were three with of mm mm mm 1 mm 0.5 mm mm pH of cells were for with 1 mm in the medium was and by of 1 mm and lactate at different concentrations in a of transport was by the transport by three with of were by of 1 of m the an of was with of scintillation and was determined in a scintillation of was used for using the was from primary cultures of neurons or astroglial cells using the to and 18: PubMed Scopus Google Scholar). was a and GeneScreen was at in × m pH 1 × mm pH mm serum with a MCT1 or MCT2 were high with 2 × at for by two of in × at were and to at with an The MCT1 and MCT2 were using and from a a MCT1 13Kim-Garcia C. Goldstein J.L. Pathak R.K. Anderson R.G.W. Brown M.S. Cell. 1994; 76: 865-873Abstract Full Text PDF PubMed Scopus (481) Google Scholar) or a MCT2 14Garcia C.K. Brown M.S. Pathak R.K. Goldstein J.L. J. Biol. Chem. 1995; 270: 1843-1849Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar). The MCT1 was obtained by reverse and chain reaction of isolated from cultured astrocytes with a of and at and in the coding of the MCT1 C. Goldstein J.L. Pathak R.K. Anderson R.G.W. Brown M.S. Cell. 1994; 76: 865-873Abstract Full Text PDF PubMed Scopus (481) Google Scholar). The MCT1 was shown to be to the mouse MCT1 L. Poole R.C. Halestrap A.P. Biophys. 1996; PubMed Scopus Google Scholar) and to with the MCT1 C. Goldstein J.L. Pathak R.K. Anderson R.G.W. Brown M.S. Cell. 1994; 76: 865-873Abstract Full Text PDF PubMed Scopus (481) Google Scholar). The MCT2 was obtained by reverse and chain reaction of isolated from mouse liver with and at and bp, in the coding of the MCT2 (14Garcia C.K. Brown M.S. Pathak R.K. Goldstein J.L. J. Biol. Chem. 1995; 270: 1843-1849Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar). The MCT2 with the MCT2 (14Garcia C.K. Brown M.S. Pathak R.K. Goldstein J.L. J. Biol. Chem. 1995; 270: 1843-1849Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar). of MCT1 was isolated from a S. A. Hamprecht B. Biochem. J. 1995; PubMed Scopus Google Scholar). The with rat MCT1 V.N. Price N.T. Halestrap A.P. Biophys. 1995; PubMed Scopus Google Scholar) was by The of MCT1 the coding was cloned the of the expression J. P. 1992; 9: Full Text PDF PubMed Scopus Google provided by the and of the Xenopus by a was with and in with in the presence of the m7G(5′)ppp(5′)G at a of 1 mm. laevis were supplied by P. and were isolated as described S. A. Hamprecht B. Biophys. 1994; PubMed Scopus Google Scholar) and allowed to were with of or of MCT1 in at a of 1 by using a of was to for and with of by at for of the mixture were to of the The were used in the to of the rat MCT1 V.N. Price N.T. Halestrap A.P. Biophys. 1995; PubMed Scopus Google to and to of oocytes with or were with of mm mm 1 1 mm 1 mm pH was at in a of the with of 14Clactate and different of Transport was different by oocytes three with of oocytes were scintillation and by of 200 of 10% of scintillation was and determined in a scintillation are for all of was when values to be was at with were by using It is well that lactate is and in mammalian cells. to this is to a reaction which is in glial cells M. I. M. Biochem. J. 234: PubMed Scopus Google Scholar). In of from lactate in primary cultures of rat glial cells at pH was found to be for an of lactate between the medium and the of the cells. of the cells with 1 the of by the of pyruvate to The of lactate not from of lactate the was and was with lactate to of lactate uptake was not the of and and low were used in all of lactate was with up to at using these the transport were determined for lactate uptake in primary cultures of rat m value of 7.7 mm and aV max value of 250 nmol/(min × mg of was determined the data were and to only was of lactate by primary cultures of rat glial cells increased with a substrate of mm, lactate uptake at pH was three at pH other monocarboxylates are also of the lactate transporter in glial cells, were an of mm transport was strongly inhibited by a of or and to a by pyruvate inhibitors of monocarboxylate transport such as α-cyano-4-hydroxycinnamate and strongly lactate uptake astroglial cells of lactate transport in astroglial cells and in Xenopus oocytes expressing transport of were with for in Hank's buffered salt at pH was determined in the at a lactate of mm in the presence or of inhibitors at for was in a with a were with of MCT1 uptake of 14Clactate was determined at a of mm in the presence or of inhibitors at for in a were with for in Hank's buffered salt at pH was determined in the at a lactate of mm in the presence or of inhibitors at for was in a with a were with of MCT1 uptake of 14Clactate was determined at a of mm in the presence or of inhibitors at for results were obtained with mouse astroglia-rich cultures. pH K m values of mm and mm and max values of nmol/(min × mg of protein), nmol/(min × mg of were determined in two max determined at pH are the max value of lactate transport in rat astroglia-rich which was determined at pH to the pH of lactate transport both types of have of lactate transport at pH Northern of MCT1 expression in primary cultures of neurons and astroglial cells revealed that MCT1 mRNA was expressed in astroglial cells with a expression in cultures The of the to that reported for rat and (12Kim C.M. Goldstein J.L. Brown M.S. J. Biol. Chem. 1992; 267: 23113-23121Abstract Full Text PDF PubMed Google Scholar). In contrast, MCT2 mRNA to be in neurons with a level of expression in astroglial cells It is the presence of three different with of and in cultures. the properties of glial lactate transport in the MCT1 was isolated from a of rat cells and cloned the expression High expression of MCT1 could be in oocytes. which were with showed a 14Clactate uptake oocytes laevis oocytes have a of 1 mm, lactate uptake was to for only Transport were determined using a of MCT1 could account for all characteristics of lactate transport in glial cells, the of glial cells and oocytes expressing MCT1 were Using 14Clactate a K m value of mm was determined in oocytes which was in agreement with the data obtained with glial cells both data max value of lactate transport in astroglia-rich cultures was and is shown in as In MCT1 expressing oocytes a with a K m value of mm was only the K m but also the pH of lactate transport in MCT1 expressing oocytes and glial cells was the data were as a a value of was for MCT1 expressing oocytes and a value of for glial cells a of the data of and were determined for glial cells and MCT1 expressing respectively. a of lactate/proton was in both of the for lactate transport in MCT1 expressing oocytes. were with of MCT1 uptake of 14Clactate was determined at different concentrations of lactate of The was at pH a with the data from the maximum velocity of lactate uptake in astroglia-rich cultures was and the is shown as a of the data gained from of lactate transport in MCT1 expressing oocytes the pH were with of MCT1 uptake of 14Clactate was determined at a of 1 mm as a of from shown as a for In the of the data a is MCT1 is a monocarboxylate which a variety of with different The action of different lactate transport was with the data obtained from glial cells Lactate transport in MCT1 expressing oocytes was strongly inhibited by and α-cyano-4-hydroxycinnamate and inhibited lactate transport in glial cells and MCT1 expressing oocytes to a were found in the of and further the of pyruvate lactate transport in MCT1 expressing the of pyruvate with lactate for uptake was concentrations mm, pyruvate not lactate uptake, whereas at concentrations mm strongly inhibited lactate transport pyruvate of mm was for of lactate The inhibited lactate transport in MCT1 expressing oocytes to an to that in glial cells the of other lactate transport in glial cells, were was isolated from rat astroglia-rich primary cultures and laevis a of lactate uptake could be determined in oocytes in to oocytes of of MCT1 in the uptake of 200 of lactate in at pH of of a lactate transport of in at pH was with to of the MCT1 the lactate uptake activity, which from the expression of glial was of MCT1 mRNA in using 2 were with of isolated from rat astroglia-rich primary or of different rat MCT1, or a mixture of of and of transport was determined in both of by the uptake of 14Clactate pH for Transport is as of The of oocytes is for in a were with of isolated from rat astroglia-rich primary or of different rat MCT1, or a mixture of of and of transport was determined in both of by the uptake of 14Clactate pH for Transport is as of The of oocytes is for Lactate transport in primary cultures of astroglial cells has been investigated by (8Nedergaard M. Goldman S.A. Am. J. Physiol. 1993; 265: R282-R289PubMed Google Scholar, J.T. McKenna M.C. Stevenson J. Couto R. Neurochem. Res. 1993; 18: 177-184Crossref PubMed Scopus (90) Google Scholar, R. Peters H. Wiesinger H. Hamprecht B. Dev. Neurosci. 1995; 17: 63-69Crossref PubMed Scopus (47) Google Scholar). The results of these studies are typical of lactate transport as described in other cell types were not detected in glial cells lactate transport was only or not inhibited by and low K m values or were these results the presence of an lactate transporter in astroglial cells. of of lactate by in and of lactate by in which allowed the of using pH was in all of the pH could not be In medium the pH of astroglial cells can be to be pH S. J. Physiol. 1994; PubMed Scopus Google Scholar). In astroglia-rich primary cultures prepared from rat of with in a by a and regulation to pH S. J. Physiol. 1994; PubMed Scopus Google Scholar). of the cell cultures with of pH in the of in a of the pH to S. J. Physiol. 1994; PubMed Scopus Google Scholar). results have been reported with astroglia-rich primary cultures from rat B. 1993; PubMed Scopus Google Scholar) and rat cerebral 1994; PubMed Scopus Google Scholar). the with in pH be and the pH can be to be to or a All were at low pH The of lactate transport in the present were in agreement with the characteristics of the monocarboxylate transporter 1 (MCT1) as determined by Carpenter and Halestrap (18Carpenter L. Halestrap A.P. Biochem. J. 1994; 304: 751-760Crossref PubMed Scopus (121) Google Scholar) in cells. The K m value of 7.7 mm determined in primary cultures is to the values determined in R.C. Halestrap A.P. Am. J. Physiol. 1993; PubMed Google Scholar), cells L. Halestrap A.P. Biochem. J. 1994; 304: 751-760Crossref PubMed Scopus (121) Google Scholar), and in cells 14Garcia C.K. Brown M.S. Pathak R.K. Goldstein J.L. J. Biol. Chem. 1995; 270: 1843-1849Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar). max values are high in primary cultures of rat or mouse astroglial cells, are the determined for other cell types R.C. Halestrap A.P. Am. J. Physiol. 1993; PubMed Google Scholar). The value of the and the of for cotransport were to the values determined for lactate transport in B. J. Membr. Biol. 1982; 70: 89-103Crossref PubMed Scopus (149) Google Scholar, R.C. Halestrap A.P. Am. J. Physiol. 1993; PubMed Google Scholar). and were found to be inhibitors of lactate transport in astroglial cells. Lactate uptake was also strongly inhibited by α-cyano-4-hydroxycinnamate and these data strongly the presence of a typical monocarboxylate transporter in astroglial cells to MCT1 of cells and pyruvate a K m value for MCT1 lactate (14Garcia C.K. Brown M.S. Pathak R.K. Goldstein J.L. J. Biol. Chem. 1995; 270: 1843-1849Abstract Full Text Full Text PDF PubMed Scopus (310) Google L. Halestrap A.P. Biochem. J. 1994; 304: 751-760Crossref PubMed Scopus (121) Google Scholar), by pyruvate was in with glial cells. the action of MCT1 was expressed laevis oocytes. of MCT1 in oocytes has been reported expression was low to the transport process (16Takanaga H. Tamai I. Inaba S. Sai Y. Higashida H. Yamamoto H. Tsuji A. Biochem. Biophys. Res. Commun. 1995; 217: 370-377Crossref PubMed Scopus (103) Google Scholar). using an expression MCT1 expression could be and allowed the investigation of transport were in of pH The pH of the oocytes was these as determined with B. J. and B. a of lactate in the an volume of be at 200 of lactate were in the the were to inhibit is in oocytes S. A. Hamprecht B. Biophys. 1994; PubMed Scopus Google Scholar). only of lactate were the which was well the of lactate transport in MCT1 expressing oocytes and glial cells revealed that lactate transport in glial cells was to be mediated by The K m the pH as well as the by α-cyano-4-hydroxycinnamate and pCMBS, were in both with a K m value was detected in MCT1 expressing oocytes. are for this of an transport system to of Biophys. J. 1995; Full Text PDF PubMed Scopus Google J. Biophys. J. 1995; Full Text PDF PubMed Scopus Google two are present transporter PubMed Scopus Google or in of transport at low concentrations or at high have been with other expressed transporters in oocytes as well S. A. Hamprecht B. Biochem. J. 1995; PubMed Scopus Google Scholar, C.L. Biophys. 1995; PubMed Scopus Google Scholar), which might a in this of the revealed that α-cyano-4-hydroxycinnamate and in MCT1 expressing oocytes and in glial cells, whereas the of and was strongly in transport in glial cells. at high concentrations was of lactate transport has been detected in astrocytes by Tildon et al. (9Tildon J.T. McKenna M.C. Stevenson J. Couto R. Neurochem. Res. 1993; 18: 177-184Crossref PubMed Scopus (90) Google Scholar). The of this data at low of the results in a K m value of mm, which is to the K m value determined in this were used to the of other in lactate of isolated from astroglia-rich primary cultures an increased lactate transport transport was by a of to different of MCT1 of not to be a of lactate The of lactate transport substrate could be by using a of a non-saturable not the is in agreement with results of Nedergaard and Goldman (8Nedergaard M. Goldman S.A. Am. J. Physiol. 1993; 265: R282-R289PubMed Google Scholar), also detected only saturable transport of lactate in These results further support the not role of MCT1 in monocarboxylate transport in astroglial cells. In agreement with the MCT1 mRNA was detected in astroglia-rich primary cultures MCT2 mRNA could be detected only In contrast, neuron-rich primary cultures expressed MCT2 mRNA at a level that MCT2 is expressed in such as liver or heart, which whereas MCT1 is for in muscle, which release lactate (20Jackson V.N. Halestrap A.P. J. Biol. Chem. 1996; 271: 861-868Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar). The data distribution of well with the distribution of lactate in the lactate isoform which is expressed in which can lactate for energy is the only isoform found in neurons Y. L. C. Magistretti P.J. J. 1996; 16: PubMed Scopus Google Scholar). In contrast, lactate isoform which is found in is expressed in astrocytes Y. L. C. Magistretti P.J. J. 1996; 16: PubMed Scopus Google Scholar). the distribution of lactate transporter and lactate in astrocytes and neurons support the that brain astrocytes neurons with the energy substrate lactate of increased energy R. R. Hamprecht B. Res. 1993; PubMed Scopus Google Scholar, P.J. L. 1996; PubMed Google Scholar). are to for also of for to use the in this modified of this was provided by