Role of age-related decrease of renal organic cation transporter 2 in the effect of atenolol on renal excretion of metformin in rats

2014 ◽  
Vol 40 (3) ◽  
pp. 349-354 ◽  
Author(s):  
Jiangxia Ren ◽  
Yan Zhou ◽  
Guoqiang Zhang ◽  
Liting Zhou ◽  
Jing Zhao ◽  
...  
2019 ◽  
Vol 104 (6) ◽  
pp. e14.2-e14
Author(s):  
N Smeets ◽  
B van Groen ◽  
J Pertijs ◽  
M Wilmer ◽  
B Smeets ◽  
...  

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


2022 ◽  
Vol 8 ◽  
Author(s):  
Chao Han ◽  
Juan Zheng ◽  
Fengyi Wang ◽  
Qingyang Lu ◽  
Qingfa Chen ◽  
...  

Organic cation transporter 2 (OCT2), encoded by the SLC22A2 gene, is the main cation transporter on the basolateral membrane of proximal tubular cells. OCT2 facilitates the entry step of the vectorial transport of most cations from the peritubular space into the urine. OCT2 downregulation in kidney disease models is apparent, yet not clear from a mechanistic vantage point. The aim of this study was to explore the role of inflammation, a common thread in kidney disease, and NF-kB in OCT2 modulation and tubular secretion. Among the OCTs, OCT2 was found consistently downregulated in the kidney of rats with chronic kidney disease (CKD) or acute kidney injury (AKI) and in patients diagnosed with CKD, and it was associated with the upregulation of TNFα renal expression. Exposure to TNFα reduced the expression and function of OCT2 in primary renal proximal tubule epithelial cells (RPTEC). Silencing or pharmacological inhibition of NF-kB rescued the expression of OCT2 in the presence of TNFα, indicating that OCT2 repression was NF-kB-dependent. In silico prediction coupled to gene reporter assay demonstrated the presence of at least one functional NF-kB cis-element upstream the transcription starting site of the SLC22A2 gene. Acute inflammation triggered by lipopolysaccharide injection induced TNFα expression and the downregulation of OCT2 in rat kidney. The inflammation did reduce the active secretion of the cation Rhodamine 123, with no impairment of the glomerular filtration. In conclusion, the NF-kB pathway plays a major role in the transcriptional regulation of OCT2 and, in turn, in the overall renal secretory capacity.


2019 ◽  
Vol 77 ◽  
pp. 105959 ◽  
Author(s):  
Qingqing Shen ◽  
Jingjing Wang ◽  
Ziqiao Yuan ◽  
Zhenzhou Jiang ◽  
Ting Shu ◽  
...  

Life Sciences ◽  
2018 ◽  
Vol 200 ◽  
pp. 63-68 ◽  
Author(s):  
Jhohann Richard de Lima Benzi ◽  
Priscila Akemi Yamamoto ◽  
Jessica Hanna Stevens ◽  
Amanda Martins Baviera ◽  
Natália Valadares de Moraes

Xenobiotica ◽  
2014 ◽  
Vol 45 (1) ◽  
pp. 88-94 ◽  
Author(s):  
Xiaonan Li ◽  
Xiaolin Sun ◽  
Jiayin Chen ◽  
Yang Lu ◽  
Yongjie Zhang ◽  
...  

2021 ◽  
pp. 114840
Author(s):  
Morena L. Sutter ◽  
Lara Console ◽  
Anne-Fleur Fahner ◽  
Sophia L. Samodelov ◽  
Zhibo Gai ◽  
...  

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