Deregulated hepsin protease activity confers oncogenicity by concomitantly augmenting HGF/MET signalling and disrupting epithelial cohesion.

Hepsin belongs to a family of cell-surface serine proteases, which have sparked interest as therapeutic targets because of the accessibility of extracellular protease domain for inhibitors. Hepsin is frequently amplified and/or overexpressed in epithelial cancers, but it is not clear how enhanced hepsin expression confers a potential for oncogenicity. We show that hepsin is consistently overexpressed in more than 40% of examined breast cancers, including all major biological subtypes. The effects of doxycycline-induced hepsin overexpression were examined in mammary epithelial organoids, and we found that induced hepsin acutely downmodulates its cognate inhibitor, hepatocyte growth factor (HGF) activator inhibitor type 1 (HAI-1). Hepsin-induced depletion of cellular HAI-1 led to a sharp increase in pericellular serine protease activity. The derepressed hepsin proteolytically activated downstream serine proteases, augmented HGF/MET signalling and caused deterioration of desmosomes and hemidesmosomes; structures important for cell cohesion and cell-basement membrane interaction. Moreover, chronic induction of hepsin considerably shortened the latency of Myc-dependent tumourigenesis in the mouse mammary gland. The serine protease and uPA system inhibitor WX-UK1, identified as a micromolar range hepsin inhibitor, prevented hepsin from augmenting HGF/MET signalling and disrupting desmosomes and hemidesmosomes. The findings suggest that the oncogenic activity of hepsin arises not only from elevated expression level but also from depletion of HAI-1, events which together trigger gain-of-function activity impacting HGF/MET signalling and epithelial cohesion. Thus, hepsin overexpression is a major oncogenic conferrer to a serine protease activity involved in breast cancer dissemination.

Physiological indicators of stress and meat and carcass characteristics in tail bitten slaughter pigs.

BACKGROUND: Tail biting is a common welfare problem in pig production and in addition to being a sign of underlying welfare problems, tail biting reduces welfare in itself. The aim of this study was to evaluate the effects of tail biting on different pre and post mortem indicators of stress in slaughter pigs and on carcass and meat characteristics. A total of 12 tail bitten (TB) and 13 control (C) pigs from a farm with a long-term tail biting problem were selected for salivary cortisol analyses before and after transport to the slaughterhouse. After stunning, samples were taken for the analysis of serum cortisol, blood lactate, intestinal heat shock protein 70 (HSP70), and meat quality characteristics. In addition, body temperature immediately after and muscle temperature 35 min after stunning were measured, as well as lean meat percentage and carcass weight. RESULTS: TB pigs showed a lower cortisol response to the transport-induced stress than C pigs and also had a lower serum cortisol concentration after stunning. HSP70 content in the small intestine was higher in the TB pigs than in C pigs. TB pigs had a considerably lower carcass weight therefore produced a lower total amount of lean meat per carcass than C pigs. CONCLUSIONS: This study suggests that prolonged or repeated stress in the form of tail biting causes a blunted stress response, possibly a sign of hypocortisolism. In addition, it underlines the importance of reducing tail biting, both from an animal welfare and an economic point-of-view.

Sequence variations and two levels of MCT1 and CD147 expression in red blood cells and gluteus muscle of horses.

MCT1-CD147 complex is the prime lactate transporter in mammalian plasma membranes. In equine red blood cells (RBCs), activity of the complex and expression of MCT1 and CD147 is bimodal; high in 70% and low in 30%. We studied whether sequence variations contribute to the bimodal expression of MCT1 and CD147. Samples of blood and cremaster muscle were collected in connection of castration from 24 horses. Additional gluteus muscle samples were collected from 15 Standardbreds of which seven were known to express low amounts of CD147 in RBCs. The cDNA of MCT1 and CD147 together with a promoter region of CD147 was sequenced. The amounts of MCT1 and CD147 expressed in RBC and muscle membranes were measured by Western blot and mRNA levels in muscles by qPCR. MCT1 and CD147 were expressed in 20 castrates, and in four only were traces found. Sequence variations found in MCT1 were not linked to MCT1 expression. In CD147 linked heterozygous single nucleotide polymorphisms (SNPs) 389A>G (Met(125)Val) and 990C>T (3'-UTR) were associated to low expression of CD147. Also a mutation 168A>G (Ile(51)Val) in CD147 was associated to low MCT1 and CD147 expression. Low MCT1 and CD147 mRNA levels in gluteus were found in Standardbreds with low CD147 expression in RBCs. The results suggest that sequence variations affect the expression level of CD147, but do not explain its bimodality. The levels of MCT1 and CD147 mRNA correlated with the expression of CD147 and suggest that bimodality of their expression is regulated at transcriptional level.

MCT1, MCT4 and CD147 gene polymorphisms in healthy horses and horses with myopathy.

Polymorphisms in human lactate transporter proteins (monocarboxylate transporters; MCTs), especially the MCT1 isoform, can affect lactate transport activity and cause signs of exercise-induced myopathy. Muscles express MCT1, MCT4 and CD147, an ancillary protein, indispensable for the activity of MCT1 and MCT4. We sequenced the coding sequence (cDNA) of horse MCT4 for the first time and examined polymorphisms in the cDNA of MCT1, MCT4 and CD147 of 16 healthy horses. To study whether signs of myopathy are linked to the polymorphisms, biopsy samples were taken from 26 horses with exercise-induced recurrent myopathy. Two polymorphisms that cause a change in amino acid sequence were found in MCT1 (Val(432)Ile and Lys(457)Gln) and one in CD147 (Met(125)Val). All polymorphisms in MCT4 were silent. Mutations in MCT1 or CD147 in equine muscle were not associated with myopathy. In the future, a functional study design is needed to evaluate the physiological role of the polymorphisms found.

Effects of age and concentrate feeding on the expression of MCT 1 and CD147 in the gastrointestinal tract of goats and Hereford finishing beef bulls.

Monocarboxylate transporter 1 (MCT 1) necessary for the absorption of short chain fatty acids in the gastrointestinal tract, was measured in ventral wall of rumen, abomasum and duodenum of kids at age of 1 day and 1, 2 and 8 weeks. Samples from rumen, abomasum and duodenum were also taken from finishing beef bulls fed concentrate either ad libitum (A) or restrictively (R). Increased expression of MCT 1 was observed during the first week and parallel increases were found in its ancillary protein, CD147 in the rumen of kids. In duodenum, MCT 1 decreased with age and a similar tendency was seen in abomasum. In bulls, MCT 1 was higher in ventral wall and atrium than in other parts of gastrointestinal tract. However, in ventral wall of rumen MCT 1 was higher in A than in R. These findings show that MCT 1 increases with the development of rumen function and also in adult animals MCT 1 may change with the feeding.

Expression of lactate transporters MCT1, MCT2 and CD147 in the red blood cells of three horse breeds: Finnhorse, Standardbred and Thoroughbred.

REASONS FOR PERFORMING STUDY: In exercising horses, up to 50% of blood lactate is taken up into red blood cells (RBCs). Lactate transporter proteins MCT1, MCT2 and CD147 (an ancillary protein for MCT1) are expressed in the equine RBC membrane. In Standardbreds (SB), lactate transport activity is bimodally distributed and correlates with the amount of MCT1 and CD147. About 75% of SB studied have high lactate transport activity in RBCs. In other breeds, the distribution of lactate transport activity is unknown. OBJECTIVES: To study whether similar bimodal distribution of MCT1 and CD147 is present also in the racing Finnhorse (FH) and Thoroughbred (TB) as in the SB and to study the distribution of MCT2 in all 3 breeds and to determine if there is a connection between MCT expression and performance markers in TB racehorses. METHODS: Venous blood samples were taken from 118 FHs, 98 TBs and 44 SBs. Red blood cell membranes were purified and MCT1, MCT2 and CD147 measured by western blot. The amount of transporters was compared with TB performance markers. RESULTS: In TBs, the distribution of MCT1 was bimodal and in all breeds distribution of MCT2 unimodal. The amount of CD147 was clearly bimodal in FH and SB, with 85 and 82% expressing high amounts of CD147. In TBs, 88% had high expression of CD147 and 11% low expression, but one horse showed intermediate expression not apparent in FH or SB. Performance markers did not correlate with the amount of MCT1, MCT2 or CD147. CONCLUSIONS: High lactate transport activity was present in all 3 racing breeds, with the greatest proportion in the TB, followed by the racing FH, then SB. There was no significant statistical correlation found between lactate transporters in RBC membrane and markers of racing performance in the TB.

Effects of training on equine muscle fibres and monocarboxylate transporters in young Coldblooded Trotters.

REASONS FOR PERFORMING STUDY: Muscular changes caused by training are breed-specific and studies on the Norwegian-Swedish Coldblooded Trotter (NSCT) are limited. Knowledge about lactate-transporters in muscle in this light draught breed used for harness racing is lacking. OBJECTIVES: To identify muscular changes associated with training in young NSCTs and investigate muscular distribution of the monocarboxylate transporter 1 (MCT1) and its ancillary protein CD147, which facilitate lactate transport across membranes. METHODS: Nine horses were followed from the start of their training period until the end of their 3-year-old season. A biopsy sample of the middle gluteal muscle was collected on 4 occasions. On the last 3 sampling occasions, individual V(La4)-values (the speed corresponding to a blood lactate concentration of 4 mmol/l) were determined in an incremental exercise test on a high-speed treadmill. One horse was excluded due to lameness. Histochemical and immunohistochemical analyses were performed on all muscle samples to determine fibre types (I, IIA, IIAX, IIX), oxidative capacity (NADH) and the expression of MCT1 and CD147. The activity of selected metabolic enzymes in the muscle before and after training was determined. RESULTS: The percentage of type IIX fibres decreased with training while the percentage of type IIAX fibres increased. The activity of citrate synthase and 3-OH-acyl-CoA-dehydrogenase increased with training. The expression of MCT1 was lower in membranes and cytoplasm of type IIX fibres compared to all other fibre types both before and after training. The antibody against CD147 stained membranes and cytoplasm of all fibres. The first V(La4)-value was lower than the last 2 in all horses. CONCLUSIONS: Muscular changes with training of NSCTs were similar to those reported in Standardbreds, indicating fibre type transitions and increased oxidative capacity. Expression of MCT1 differed among fibre types and was related to the oxidative capacity of the fibres.

Immunohistochemical analysis of MCT1 and CD147 in equine skeletal muscle fibres.

Monocarboxylate transporter 1 (MCT1) and its ancillary protein CD147 facilitate efflux of lactate from the muscle. Expression of MCT1 and CD147 were studied with immunohistochemistry in type I, IIA, IIAB and IIB fibres of equine gluteal muscle. Staining intensity of MCT1 in the cytoplasm as well as in the membranes of fibre types decreased in the order I=IIA>IIAB>IIB and correlated with the oxidative capacity. Capillaries were pronounced in the MCT1 staining. CD147 antibody stained plasma membranes of all fibre types evenly, whereas the staining in the cytoplasm followed that of MCT1. In the middle gluteal muscle the expression of MCT1 follows the oxidative capacity of muscle fibres, but the expression of CD147 in sarcolemma does not vary among fibre types. The use of horse specific MCT1 and CD147 antibodies can in future studies help to evaluate lactate efflux from different muscle fibre types.

Plasma levels of heat shock protein 72 (HSP72) and beta-endorphin as indicators of stress, pain and prognosis in horses with colic.

A prospective observational study was performed to evaluate whether the plasma concentration of heat shock protein 72 (HSP72) or beta-endorphin is related to clinical signs, blood chemistry, or severity of pain of colic. Seventy-seven horses with colic and 15 clinically healthy controls were studied. The horses were divided into four groups which reflected increasing severity of colic, from normal control horses to horses with mild, moderate and severe colic. Blood samples were collected before any treatment. Packed cell volume (PCV) and plasma HSP72, beta-endorphin, cortisol, adrenocorticotropic hormone (ACTH) and lactate concentrations were measured. Plasma beta-endorphin was related with severity of colic and survival, as well as with plasma cortisol, ACTH and lactate concentrations, heart rate, PCV and pain score. High plasma HSP72 concentration may indicate circulatory deficits, but was not associated with clinical signs of colic. Plasma lactate still seemed to be the most useful single prognostic parameter in horses with colic.

Lactate transport in canine red blood cells.

OBJECTIVE: To detect monocarboxylate transporters (MCTs) in canine RBC membranes and to determine the distribution of lactate between plasma and RBCs. SAMPLE POPULATION: Blood samples obtained from 6 purpose-bred Beagles. PROCEDURES: Monocarboxylate transporter isoforms 1, 2, 4, 6, 7, and 8 and CD147 were evaluated in canine RBCs by use of western blot analysis. Lactate influx into RBCs was measured as incorporation of radioactive lactate. RESULTS: 2 MCT isoforms, MCT1 and MCT7, were detected in canine RBC membranes on western blot analysis, whereas anti-MCT2, anti-MCT4, anti-MCT6, and anti-MCT8 antibodies resulted in no signal. No correlation was found between the amount of MCT1 or MCT7 and lactate transport activity, but the ancillary protein CD147 that is needed for the activity of MCT1 had a positive linear correlation with the rate of lactate influx. The apparent Michael is constant for the lactate influx in canine RBCs was 8.8 +/- 0.9mM. Results of in vitro incubation studies revealed that at lactate concentrations of 5 to 15mM, equilibrium of lactate was rapidly obtained between plasma and RBCs. CONCLUSIONS AND CLINICAL RELEVANCE: These results indicated that at least half of the lactate transport in canine RBCs occurs via MCT1, whereas MCT7 may be responsible for the rest, although an additional transporter was not ruled out. For practical purposes, the rapid equilibration of lactate between plasma and RBCs indicated that blood lactate concentrations may be estimated from plasma lactate concentrations.

Ultrasound transmission technique as a potential tool for physical evaluation of monolithic matrix tablets.

The aim of this study was to investigate the effects of tablet porosity and particle size fraction of compacted Starch acetate powders, with and without model drug caffeine, on acoustic properties of tablets. The ultrasound velocity was determined from the transmission measurements. Tablets of starch acetate (SA DS 2.7) powder with two particle size fractions of 0-53 and 0-710 microm were compressed with a compaction simulator. Porosities of tablets varied in the range from 12% to 43% for both particle size fractions. Strong associations were found between the ultrasound velocity and physical properties of the tablets such as porosity and particle size fraction. Interestingly, ultrasound velocity was practically insensitive to inclusion of the model drug caffeine with the concentrations used. Based on this study ultrasound transmission method is a potential non-destructive tool for studying structural changes of tablets and other solid dosage forms.

Targeting the cannabinoid CB2 receptor: modelling and structural determinants of CB2 selective ligands.

Recent developments indicate that CB2 receptor ligands have the potential to become therapeutically important. To explore this potential, it is necessary to develop compounds with high affinity for the CB2 receptor and little affinity for the CB1 receptor. This review will discuss structure-activity relations at both receptors for classical cannabinoids and cannabimimetic indoles. Examples of CB2 selective ligands from both classes of compounds are presented and the structural features leading to selectivity are described. Two approaches, receptor mutations and molecular modelling, have been employed to investigate the interaction of ligands with both cannabinoid receptors. These results obtained from these techniques are discussed.

Identification of inhibitors of the nicotine metabolising CYP2A6 enzyme--an in silico approach.

The compulsive nature of tobacco use is attributable to nicotine addiction. Nicotine is eliminated by metabolism through the cytochrome P450 2A6 (CYP2A6) enzyme in liver. Inhibition of CYP2A6 by chemical compounds may represent a potential supplement to anti-smoking therapy. The purpose of this study was to rationally design potent inhibitors of CYP2A6. 3D-QSAR models were constructed to find out which structural characteristics are important for inhibition potency. Specifically located hydrophobic and hydrogen donor features were found to affect inhibition potency. These features were used in virtual screening of over 60,000 compounds in the Maybridge chemical database. A total of 22 candidate molecules were selected and tested for inhibition potency. Four of these were potent and selective CYP2A6 inhibitors with IC(50) values lower than 1 muM. They represent novel structures of CYP2A6 inhibitors, especially N1-(4-fluorophenyl)cyclopropane-1-carboxamide. This compound can be used as a lead in the design of CYP2A6 inhibitor drugs to combat nicotine addiction.

New potent and selective cytochrome P450 2B6 (CYP2B6) inhibitors based on three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis.

BACKGROUND AND PURPOSE: The cytochrome P450 2B6 (CYP2B6) enzyme metabolises a number of clinically important drugs. Drug-drug interactions resulting from inhibition or induction of CYP2B6 activity may cause serious adverse effects. The aims of this study were to construct a three-dimensional structure-activity relationship (3D-QSAR) model of the CYP2B6 protein and to identify novel potent and selective inhibitors of CYP2B6 for in vitro research purposes. EXPERIMENTAL APPROACH: The inhibition potencies (IC(50) values) of structurally diverse chemicals were determined with recombinant human CYP2B6 enzyme. Two successive models were constructed using Comparative Molecular Field Analysis (CoMFA). KEY RESULTS: Three compounds proved to be very potent and selective competitive inhibitors of CYP2B6 in vitro (IC(50)<1 microM): 4-(4-chlorobenzyl)pyridine (CBP), 4-(4-nitrobenzyl)pyridine (NBP), and 4-benzylpyridine (BP). A complete inhibition of CYP2B6 activity was achieved with 0.1 microM CBP, whereas other CYP-related activities were not affected. Forty-one compounds were selected for further testing and construction of the final CoMFA model. The created CoMFA model was of high quality and predicted accurately the inhibition potency of a test set (n=7) of structurally diverse compounds. CONCLUSIONS AND IMPLICATIONS: Two CoMFA models were created which revealed the key molecular characteristics of inhibitors of the CYP2B6 enzyme. The final model accurately predicted the inhibitory potencies of several structurally unrelated compounds. CBP, BP and NBP were identified as novel potent and selective inhibitors of CYP2B6 and CBP especially is a suitable inhibitor for in vitro screening studies.

Expression of CD147 and monocarboxylate transporters MCT1, MCT2 and MCT4 in porcine small intestine and colon.

Lactate, formed mainly in the stomach and small intestines, and short-chain fatty acids (SCFAs) formed in the colon, are ionised and require transporter proteins such as monocarboxylate transporters (MCTs) for absorption. The amounts of MCT1, MCT2, MCT4 and CD147, an ancillary protein for MCT1 and MCT4, were measured by immunoblotting the small intestine and colon of 40 pigs (Landrace, Yorkshire and LandracexYorkshire). MCT1 and MCT4 were found in both small intestine and colon, but MCT2 only in the small intestine. In both small intestine and colon, Yorkshire pigs had more CD147 than Landrace pigs, while no interbreed differences were found in MCT isoforms. Since CD147 is essential for the activity of MCT1 and MCT4, the breed difference suggests that MCT activity is higher in Yorkshire than in Landrace pigs. The absence of MCT2 in the colon suggests that it is mainly a lactate transporter, while MCT1 and MCT4 facilitate the transport of both lactate and SCFA.

The inducible form of heat shock protein 70 in the serum, colon and small intestine of the pig: comparison to conventional stress markers.

Modern rearing conditions may cause stress to pigs. At the cellular level all animals respond to stress by synthesizing heat shock proteins (HSP), which protect cells from injury. The objective of this study was to examine the concentrations of stress-inducible HSP72 in porcine small intestine and colon, known to be stress sensitive tissues, and to compare the findings with HSP72 concentrations in serum and with conventional markers of stress, namely blood lactate and serum cortisol, glucose, free fatty acids and acute phase proteins. HSP72 in the colon correlated with serum HSP72 but there was a negative correlation with carcass weight (growth). The results suggest that the colon may be a significant source of serum HSP72, the concentration of which may reflect changes in the permeability of intestinal epithelium due to stressors, such as transport and handling.

MCT1 and CD147 gene polymorphisms in standardbred horses.

REASONS FOR PERFORMING STUDY: Transport of lactate across membranes is facilitated by proton-monocarboxylate transporters (MCT). The most widely distributed isoform is MCT1, which needs an ancillary protein CD147. Studies on erythrocytes have shown that high activity of MCT1 is inherited as the dominant allele and that activity is regulated through CD147. Mutations of human MCT1 have been described that appear to impair lactate transport in muscles and cause exertional rhabdomyolysis. There are no reports of this potential relationship in the horse. OBJECTIVES: To obtain sequences of equine MCT1 and CD147 to examine differences between horses with high and low lactate transport activity in their erythrocytes. METHODS: Muscle biopsy samples were taken from 3 healthy Standardbred horses and from 7 horses which according to the owners had signs of myopathy after intense exercise. DNA and RNA were isolated and PCR analysis and sequencing performed. RESULTS: Currently, PCR fragments covering 100% of MCT1 and 70% of CD147 coding region are retained and sequence analysis has demonstrated one single nucleotide polymorphism (SNP) in the C-terminal area of MCT1 and one SNP in the extracellular domain of CD147. Both cause an amino acid change. The SNPs found are not related to lactate transport activity in erythrocytes or signs of myopathy. CONCLUSIONS: More samples need to be analysed to make conclusions on the significance of the polymorphisms found. Furthermore, full sequence coverage of the coding region of CD147 is needed. POTENTIAL RELEVANCE: The molecular probes produced could be used as tools to study gene regulation of lactate transport.

Monocarboxylate transporters (MCT) as lactate carriers in equine muscle and red blood cells.

REASONS FOR PERFORMING STUDY: Monocarboxylate transporters (MCT) facilitate the transport of lactate across membranes. In red blood cells (RBC) the transport activity varies interindividually due to differences in the amount of an ancillary protein CD147. Similar variations in muscles could have a great influence on lactate accumulation during exercise. OBJECTIVES: To study the expression of MCT isoforms and CD147 in the middle gluteal muscle. METHODS: Venous blood and muscle biopsy samples were taken from 14 Standardbred horses. Lactate transport activity in RBC and the amounts of MCT1, 2, 4 and CD147 were measured. RESULTS: In muscle MCT1, MCT4 and CD147 were found. Amount of MCT1 was variable and not dependent on age or training. Expression of MCT4 increased with age and correlated positively with CD147. CD147 in muscle correlated with that in RBC. MCT4 in muscle and CD147/MCT1 in RBC were higher in race fit than in moderately trained horses. CONCLUSIONS: MCT isoform profile in equine muscle is similar to that in man. The correlation between CD147 in muscle and RBC supports the view that lactate transport activity in muscles may vary interindividually as with RBC. POTENTIAL RELEVANCE: A larger number of horses need to be analysed to confirm the relationship of CD147 in muscle and RBC; and to allow the use the lactate transport activity in RBC as an indicator of the respective activity in muscles.

The effect of powder blend and tablet structure on drug release mechanisms of hydrophobic starch acetate matrix tablets.

This study investigates the release mechanism of a hydrophilic drug (caffeine) from hydrophobic matrix tablets composed of starch acetate. Different particle size fractions of starch acetate were mixed with caffeine (22% V/V) to obtain various mixture organisations in the powder, as well as in the final tablet. The organisation of powder mixtures was calculated by the carrier payload of starch acetate particles, while the pore size distributions in tablets were measured by mercury intrusion porosimetry. A carrier payload below 1 indicated the existence of a free starch acetate particle surface, while numbers greater than 1 pointed to a complete occupation of the starch acetate particle surface area by caffeine particles. The carrier payload calculations gave a good prediction for the existence of a starch acetate matrix in the tablet structures. Caffeine matrices in tablets compressed from the mixtures could be detected by mercury intrusion porosimetry measurements. The existence of different matrices, as well as different pore networks, determined the physical changes of the tablets and the release mechanism of caffeine during dissolution tests. When a tablet contained only a caffeine matrix, rapid tablet disintegration and immediate release of the total amount of caffeine occurred. A single matrix of starch acetate resulted in tablets that remained intact, although cracks were formed. The co-existence of matrices of both materials created surface erosion of the tablet. The caffeine release profiles of tablets that remained intact or showed erosion were fitted by an equation containing both diffusional and relaxational factors to describe the effect of tablet porosity on drug release.

Expression of MCT1, MCT2 and MCT4 in the rumen, small intestine and liver of reindeer (Rangifer tarandus tarandus L.).

The expression of monocarboxylate transporters MCT1, MCT2 and MCT4 in the rumen, small intestine and liver was examined in free-ranging and captive reindeer. In addition, expression of chaperone protein CD147, which is needed for the activity of MCT1 and MCT4, was studied in the rumen of suckling calves. Immunoblotting of cell membrane proteins showed the expression of MCT1 and MCT4, but not that of MCT2 in the rumen of reindeer. In free-ranging reindeer the amount of MCT1 was higher than in the captive ones (P<0.01). Developing rumen of suckling calves expressed MCT1 and MCT4 and positive correlation was found between MCT1 and CD147. Both MCT1 and CD147 correlated also with age in calves less than 10 days. In the small intestine all the isoforms studied were expressed, but the amounts were lower than in the rumen (P<0.05). In the liver MCT1 and MCT2 were found while MCT4 was nearly undetectable. The expression of MCT isoforms in the rumen and small intestine reflects the site of absorption and concentrations of short chain fatty acids (SCFA). In the liver the expression of high affinity transporters, MCT1 and MCT2, is in accordance with almost complete uptake of propionate from portal blood.