scholarly journals Carnitine/organic cation transporter OCTN2-mediated transport of carnitine in primary-cultured epididymal epithelial cells

Reproduction ◽  
2005 ◽  
Vol 130 (6) ◽  
pp. 931-937 ◽  
Author(s):  
Daisuke Kobayashi ◽  
Masanori Irokawa ◽  
Tomoji Maeda ◽  
Akira Tsuji ◽  
Ikumi Tamai
Keyword(s):  
Epithelial Cells ◽  
Organic Cation ◽  
Basolateral Membrane ◽  
Organic Cation Transporter ◽  
Systemic Circulation ◽  
Transport Systems ◽  
Pcr Analysis ◽  
Carnitine Transporter ◽  
Carnitine Transport ◽  
Cationic Compounds

Carnitine is essential for the acquisition of motility and maturation of spermatozoa in the epididymis, and is accumulated in epididymal fluid. In this study, carnitine transport into primary-cultured rat epididymal epithelial cells was characterized to clarify the nature of the transporter molecules involved. Uptake of carnitine by primary-cultured epididymal epithelial cells was time, Na+and concentration dependent. Kinetic analysis of carnitine uptake by the cells revealed the involvement of high- and low-affinity transport systems withKm values of 21 μM and 2.2 mM respectively. The uptake of carnitine by the cells was significantly reduced by inhibitors of carnitine/organic cation transporter (OCTN2), such as carnitine analogues and cationic compounds. In RT-PCR analysis, OCTN2 expression was detected. These results demonstrated that the high-affinity carnitine transporter OCTN2, which is localized at the basolateral membrane of epididymal epithelial cells, mediates carnitine supply into those cells from the systemic circulation as the first step of permeation from blood to spermatozoa.

scholarly journals Organic Cation Transporter 1 an Intestinal Uptake Transporter: Fact or Fiction?

2021 ◽  
Vol 12 ◽  
Author(s):  
Christoph Wenzel ◽  
Marek Drozdzik ◽  
Stefan Oswald
Keyword(s):  
Cellular Localization ◽  
Organic Cation ◽  
Basolateral Membrane ◽  
Organic Cation Transporter ◽  
Systemic Circulation ◽  
Current Evidence ◽  
Human Intestine ◽  
Intestinal Uptake ◽  
Organic Cation Transporter 1

Intestinal transporter proteins are known to affect the pharmacokinetics and in turn the efficacy and safety of many orally administered drugs in a clinically relevant manner. This knowledge is especially well-established for intestinal ATP-binding cassette transporters such as P-gp and BCRP. In contrast to this, information about intestinal uptake carriers is much more limited although many hydrophilic or ionic drugs are not expected to undergo passive diffusion but probably require specific uptake transporters. A transporter which is controversially discussed with respect to its expression, localization and function in the human intestine is the organic cation transporter 1 (OCT1). This review article provides an up-to-date summary on the available data from expression analysis as well as functional studies in vitro, animal findings and clinical observations. The current evidence suggests that OCT1 is expressed in the human intestine in small amounts (on gene and protein levels), while its cellular localization in the apical or basolateral membrane of the enterocytes remains to be finally defined, but functional data point to a secretory function of the transporter at the basolateral membrane. Thus, OCT1 should not be considered as a classical uptake transporter in the intestine but rather as an intestinal elimination pathway for cationic compounds from the systemic circulation.

scholarly journals Regulation Mechanisms of Expression and Function of Organic Cation Transporter 1

2021 ◽  
Vol 11 ◽  
Author(s):  
Giuliano Ciarimboli
Keyword(s):  
Organic Cation ◽  
Basolateral Membrane ◽  
Organic Cation Transporter ◽  
Organic Cations ◽  
Regulatory Processes ◽  
Organic Cation Transporter 1 ◽  
Exogenous Origin ◽  
And Function

The organic cation transporter 1 (OCT1) belongs together with OCT2 and OCT3 to the solute carrier family 22 (SLC22). OCTs are involved in the movement of organic cations through the plasma membrane. In humans, OCT1 is mainly expressed in the sinusoidal membrane of hepatocytes, while in rodents, OCT1 is strongly represented also in the basolateral membrane of renal proximal tubule cells. Considering that organic cations of endogenous origin are important neurotransmitters and that those of exogenous origin are important drugs, these transporters have significant physiological and pharmacological implications. Because of the high expression of OCTs in excretory organs, their activity has the potential to significantly impact not only local but also systemic concentration of their substrates. Even though many aspects governing OCT function, interaction with substrates, and pharmacological role have been extensively investigated, less is known about regulation of OCTs. Possible mechanisms of regulation include genetic and epigenetic modifications, rapid regulation processes induced by kinases, regulation caused by protein–protein interaction, and long-term regulation induced by specific metabolic and pathological situations. In this mini-review, the known regulatory processes of OCT1 expression and function obtained from in vitro and in vivo studies are summarized. Further research should be addressed to integrate this knowledge to known aspects of OCT1 physiology and pharmacology.

scholarly journals OCTN2-mediated transport of carnitine in isolated Sertoli cells

Reproduction ◽  
2005 ◽  
Vol 129 (6) ◽  
pp. 729-736 ◽  
Author(s):  
Daisuke Kobayashi ◽  
Akihiko Goto ◽  
Tomoji Maeda ◽  
Jun-ichi Nezu ◽  
Akira Tsuji ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Pcr Analysis ◽  
Rt Pcr ◽  
Carnitine Transporter ◽  
High Affinity ◽  
Carnitine Transport ◽  
Testis Tissue ◽  
Blood Testis Barrier

Carnitine is extensively accumulated in epididymis. Carnitine is also accumulated in testis at higher concentration than in the plasma and is used in spite of the presence of the blood–testis barrier. In this study, we examined the characteristics of carnitine transport in primary-cultured rat Sertoli cells, which constitute a part of the blood–testis barrier. Uptake of [3H]carnitine (11.4 nM) from the basal side of Sertoli cells was Na+-dependent and was significantly decreased in the presence of 10 μM (48.0 ± 7.4% of control) or 100 μM unlabeled carnitine (14.6 ± 5.7% of control). Furthermore, the uptake was significantly inhibited in the presence of 100 μM acetyl-L-carnitine, 100 μM gamma-butyrobetaine or 500 μM quinidine. In RT-PCR analysis, the high-affinity carnitine transporter OCTN2 was detected in rat whole testis tissue and primary-cultured Sertoli cells. In contrast, the low-affinity carnitine transporter ATB0,+was detected in rat whole testis tissue, but not in primary cultured Sertoli cells. These results demonstrate that OCTN2 mediates carnitine supply to Sertoli cells from the circulation.

Daunomycin secretion by killfish renal proximal tubules

1995 ◽  
Vol 269 (2) ◽  
pp. R370-R379 ◽  
Author(s):  
D. S. Miller
Keyword(s):  
Organic Cation ◽  
Basolateral Membrane ◽  
Organic Cation Transporter ◽  
Proximal Tubules ◽  
Epifluorescence Microscopy ◽  
Buffer Solution ◽  
Simple Diffusion ◽  
Renal Proximal Tubules ◽  
Cellular Accumulation ◽  
Tubular Lumen

Epifluorescence microscopy and video-image analysis were used to measure the uptake of the fluorescent anthracycline daunomycin by intact killifish renal proximal tubules. When tubules were incubated in medium containing 2-5 microM daunomycin, the drug accumulated in the cells and the tubular lumen. At steady state, luminal fluorescence was two to three times greater than cellular fluorescence. Luminal accumulation of daunomycin was reduced when tubules were exposed to the multidrug-resistance (MDR) transporter modifiers verapamil and cyclosporin A (CSA), but not tetraethylammonium (TEA), a model substrate for the renal organic cation transport system. NaCN and vanadate reduced luminal drug accumulation. In contrast, cellular daunomycin accumulation was not affected by verapamil, CSA, TEA, or vanadate and was only slightly reduced by NaCN. When the pH of the buffer solution was decreased from 8.25 to 7.25, luminal, but not cellular, accumulation of daunomycin was again reduced by CSA; however, TEA now reduced cellular and luminal accumulation. These findings are consistent with daunomycin being actively secreted in killifish proximal tubule by two mechanisms. At pH 8.25, daunomycin crossed the basolateral membrane by simple diffusion and was secreted into the tubular lumen by the MDR transporter. At pH 7.25, daunomycin was transported across the basolateral membrane by simple diffusion and carrier-mediated uptake on the organic cation transporter and was secreted into the lumen by the MDR transporter and the organic cation/H+ exchanger.

scholarly journals O32 Ontogeny of human kidney OCT2 expression across the paediatric age range

2019 ◽  
Vol 104 (6) ◽  
pp. e14.2-e14
Author(s):  
N Smeets ◽  
B van Groen ◽  
J Pertijs ◽  
M Wilmer ◽  
B Smeets ◽  
...  
Keyword(s):  
Organic Cation ◽  
Basolateral Membrane ◽  
Age Groups ◽  
Kidney Tissue ◽  
Human Kidney ◽  
Organic Cation Transporter ◽  
Age Related ◽  
Paediatric Age ◽  
Organic Cation Transporter 2 ◽  
Related Pattern

BackgroundIn adults, the organic cation transporter 2 (protein name OCT2, gene name SLC22A2) is localised in the kidney proximal tubules where it mediates organic cation secretion. Hence, the transporter plays a role in the disposition and excretion of several drugs and drug-drug interactions. To better understand the disposition of OCT2 substrate drugs in children, we studied OCT2 localisation and expression in paediatric kidney tissue.MethodsThe expression of OCT2 was visualised in tissue using immunohistochemical staining. Tissues were derived post-mortem from children aged 0 -14 years. Gestational age varied between 24 and 40 weeks. Intensity of the staining at the basolateral membrane was scored by two individual observers using three categories; negative, detectible and high. Agreement between two observers was determined using Cohen’s kappa.Results44 kidney samples (n=17 neonates, n=17 infants, n=7 children, n=3 adolescent) were analysed and scored. There was substantial agreement between two judgements with a kappa of 0.773 (p< 0.005). No age related pattern was observed in the expression of OCT2. Even in the youngest age group, the expression of OCT2 was clearly visible.ConclusionThe kidney expression of OCT2 did not show an age-related pattern. In all age groups, expression levels were similar and OCT2 was properly localised at the basolateral membrane. These findings suggest that, with increasing age, OCT2 will not influence the renal excretion of its substrates.Disclosure(s)Nothing to disclose

scholarly journals Role of σB in Regulating the Compatible Solute Uptake Systems of Listeria monocytogenes: Osmotic Induction of opuC Is σB Dependent

2003 ◽  
Vol 69 (4) ◽  
pp. 2015-2022 ◽  
Author(s):  
Katy R. Fraser ◽  
David Sue ◽  
Martin Wiedmann ◽  
Kathryn Boor ◽  
Conor P. O'Byrne
Keyword(s):  
Listeria Monocytogenes ◽  
Solute Transport ◽  
Compatible Solutes ◽  
Strain Analysis ◽  
Compatible Solute ◽  
Transport Systems ◽  
Carnitine Transporter ◽  
Solute Uptake ◽  
Carnitine Transport

ABSTRACT The regulation of the compatible solute transport systems in Listeria monocytogenes by the stress-inducible sigma factor σB was investigated. Using wild-type strain 10403S and an otherwise isogenic strain carrying an in-frame deletion in sigB, we have examined the role of σB in regulating the ability of cells to utilize betaine and carnitine during growth under conditions of hyperosmotic stress. Cells lacking σB were defective for the utilization of carnitine but retained the ability to utilize betaine as an osmoprotectant. When compatible solute transport studies were performed, the initial rates of uptake of both betaine and carnitine were found to be reduced in the sigB mutant; carnitine transport was almost abolished, whereas betaine transport was reduced to approximately 50% of that of the parent strain. Analysis of the cytoplasmic pools of compatible solutes during balanced growth revealed that both carnitine and betaine steady-state pools were reduced in the sigB mutant. Transcriptional reporter fusions to the opuC (which encodes an ABC carnitine transporter) and betL (which encodes an a secondary betaine transporter) operons were generated by using a promoterless copy of the gus gene from Escherichia coli. Measurement of β-glucuronidase activities directed by opuC-gus and betL-gus revealed that transcription of opuC is largely σB dependent, consistent with the existence of a potential σB consensus promoter motif upstream from opuCA. The transcription of betL was found to be sigB independent. Reverse transcriptase PCR experiments confirmed these data and indicated that the transcription of all three known compatible solute uptake systems (opuC, betL, and gbu), as well as a gene that is predicted to encode a compatible solute transporter subunit (lmo1421) is induced in response to elevated osmolarity. The osmotic induction of opuCA and lmo1421 was found to be strongly σB dependent. Together these observations suggest that σB plays a major role in the regulation of carnitine utilization by L. monocytogenes but is not essential for betaine utilization by this pathogen.

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