Disease relevance of Slc22a5

• Furthermore, our RT-PCR analyses reveal the presence of mRNA for novel organic cation transporters 1 and 2 (OCTN1 and OCTN2), but not for OCT1 or OCT2 in the ganglion [1].
• We utilized adenovirus vectors for efficient gene transfer of trophic factors (glial-cell derived neurotrophic factor [GDNF] and cardiotrophin-1 [CT-1]) or calbindin-D28k [2].
• HYPOTHESIS: Administration of cardiotrophin 1 (CT-1) can treat experimental fulminant hepatic failure (FHF) [3].
• The original report by Pennica et al. on Cardiotrophin-1 (CT-1) states that it markedly stimulates hypertrophy in cardiac myocytes both in vitro and in vivo and is predominantly expressed in the early mouse embryonic heart tube [4].

High impact information on Slc22a5

• The beta-lactam antibiotics cephaloridine, cefoselis, cefepime, and cefluprenam were found to inhibit OCTN2-mediated carnitine transport [5].
• The interaction of cephaloridine with OCTN2 is competitive with respect to carnitine [5].
• We investigated the interaction of several beta-lactam antibiotics with OCTN2 using human cell lines that express the transporter constitutively as well as using cloned human and rat OCTN2s expressed heterologously in human cell lines [5].
• These studies show that OCTN2 plays a crucial role in the pharmacokinetics and therapeutic efficacy of certain beta-lactam antibiotics such as cephaloridine and that cephaloridine-induced carnitine deficiency is likely to be due to inhibition of carnitine reabsorption in the kidney [5].
• OBJECTIVES: We investigated whether autologous transplantation of skeletal myoblasts (MB) transferred with cardiotrophin-1 (CT-1) gene could retard the transition to heart failure (HF) in Dahl salt-sensitive (DS) hypertensive rats [6].

Biological context of Slc22a5

• Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter [7].
• Furthermore, the uptake of acetyl-L-[3H]carnitine by the BCECs of juvenile visceral steatosis (jvs) mouse, in which OCTN2 is functionally defective owing to a genetical missense mutation of one amino acid residue, was reduced [8].
• A 1.9-kilobase OCTN2 cDNA from rat epididymis was amplified by reverse transcription polymerase chain reaction (RT-PCR) and cloned [9].
• CONCLUSION: These findings suggest a downregulation of OCTN2 at the renal level, in the presence of high levels of carnitine [10].
• Screening of a cDNA library from RBE4 cells with rat OCTN2 cDNA as a probe identified a positive clone which showed, when expressed in HeLa cells, the functional characteristics of OCTN2 [11].

Anatomical context of Slc22a5

• CT1 mRNA was strongly expressed in the testis, colon, kidney, and liver and weakly in the skeletal muscle, placenta, small intestine, and brain [12].
• When expressed in Xenopus oocytes, CT1 mediated a high-affinity transport of L-carnitine (Km = 25 microM) [12].
• In situ hybridization in the rat shows that OCTN2 is expressed in the proximal and distal tubules and in the glomeruli in the kidney, in the myocardium, valves, and arterioles in the heart, in the labyrinthine layer of the placenta, and in the cortex, hippocampus, and cerebellum in the brain [7].
• Functional relevance of carnitine transporter OCTN2 to brain distribution of L-carnitine and acetyl-L-carnitine across the blood-brain barrier [8].
• Immunohystochemical analysis showed that OCTN3 protein was mainly associated with the basolateral membrane of rat and chicken enterocytes, whereas OCTN2 was detected at the apical membrane [13].

Associations of Slc22a5 with chemical compounds

• The replacement of extracellular sodium with Li reduced CT1-mediated L-carnitine uptake to 19.8% [12].
• CT1 did not transport typical substrates for either organic anion or organic cation transporters, such as p-aminohippurate and tetraethylammonium [12].
• Octanoylcarnitine, acetylcarnitine, and gamma-butyrobetaine showed potent inhibitory effects on CT1-mediated L-carnitine uptake; betaine and d-carnitine showed moderate inhibition [12].
• Simvastatin was proved, in a dose-independent manner, to decrease cardiacmyocytes size as well as protein synthesis, and inhibit ANP mRNA synthesis and JAK-STAT protein expression induced by CT-1 in cardiacmyocytes.Conclusion: These results suggest that simvastatin can ameliorate cardiacmyocytes hypertrophyin vitrovia JAK-STAT signaling pathways [14].
• OCTN2 transports organic cations without involving Na(+), but it transports carnitine only in the presence of Na(+) [7].

Other interactions of Slc22a5

• Cardiotrophin-1 (CT-1) is a cytokine involved in the growth and survival of cardiac cells via activation of the Janus activated kinase/signal transducer activator of transcription (JAK/STAT) [14].
• An increased mRNA expression following partial hepatectomy was detected for organic anion transporting polypeptide (Oatp)5, Octn1, Octn2 and SGLT2 [15].
• We speculate that ALCAR may operate through interference with organic cation transporters such as OCTN2 and/or carnitine-acylcarnitine translocase (CACT), based partly on the above findings and on semi-empirical electronic similarity calculations on ALCAR, MPP+, and two other substrates for these transporters [16].
• The aim of this study was to investigate whether the concomitant administration of the substrates or inhibitors of PEPT1, OCTN1, OCTN2, and P-glycoprotein affects the intestinal absorption of sulpiride in rats [17].

Analytical, diagnostic and therapeutic context of Slc22a5

• OCTN2 was confirmed to be expressed in rat and human BCECs by an RT-PCR method [8].
• To localize the protein, an antibody raised against a carboxy-terminal peptide of OCTN2 was produced in rabbits and used for Western blot analysis and immunohistochemistry [9].
• Kinetic parameters of L-carnitine uptake were calculated by non-linear regression, and the relative abundance of the carnitine transporter, OCTN2, was determined by Western blot analysis [10].
• Molecular cloning and functional characterization of the OCTN2 transporter at the RBE4 cells, an in vitro model of the blood-brain barrier [11].
• These results clarified that OCTN2 is important for the concentrative reabsorption of L-carnitine after glomerular filtration in the kidney [18].

References