ROLE OF ORGANIC ANION TRANSPORTER OATP1B1 (OATP-C) IN HEPATIC UPTAKE OF IRINOTECAN AND ITS ACTIVE METABOLITE, 7-ETHYL-10-HYDROXYCAMPTOTHECIN: IN VITRO EVIDENCE AND EFFECT OF SINGLE NUCLEOTIDE POLYMORPHISMS

2004 ◽  
Vol 33 (3) ◽  
pp. 434-439 ◽  
Author(s):  
Takashi Nozawa ◽  
Hironobu Minami ◽  
Shigeki Sugiura ◽  
Akira Tsuji ◽  
Ikumi Tamai
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Active Metabolite ◽  
Organic Anion ◽  
Hepatic Uptake ◽  
Organic Anion Transporter ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Anion Transporter

Role of Hepatic Organic Anion Transporter 2 in the Pharmacokinetics ofR- andS-Warfarin: In Vitro Studies and Mechanistic Evaluation

2018 ◽  
Vol 15 (3) ◽  
pp. 1284-1295 ◽  
Author(s):  
Yi-an Bi ◽  
Jian Lin ◽  
Sumathy Mathialagan ◽  
Laurie Tylaska ◽  
Ernesto Callegari ◽  
...  
Keyword(s):  
Organic Anion ◽  
In Vitro Studies ◽  
Organic Anion Transporter ◽  
Anion Transporter

scholarly journals Frequencies of Single-Nucleotide Polymorphisms and Haplotypes of the SLCO1B1 Gene in Selected Populations of the Western Balkans

2015 ◽  
Vol 18 (1) ◽  
pp. 5-22 ◽  
Author(s):  
A. Daka Grapci ◽  
A. J. Dimovski ◽  
A. Kapedanovska ◽  
M. Vavlukis ◽  
A. Eftimov ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Ethnic Groups ◽  
Organic Anion ◽  
Nucleotide Polymorphisms ◽  
Western Balkans ◽  
Single Nucleotide ◽  
Anion Transporter ◽  
Significant Difference ◽  
Variant Alleles ◽  
Slco1b1 Gene

Abstract As a membrane influx transporter, organic anion- transporting polypeptide 1B1 (OATP1B1) regulates the cellular uptake of a number of endogenous compounds and drugs. The aim of this study was to characterize the diversity of the solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene encoding this transporter in two ethnic groups populating the Western Balkans. The distribution of SCLO1B1 alleles was determined at seven variant sites (c.388A>G, c.521T>C, c.571T>C, c.597C>T, c.1086C>T, c.1463G>C and c.*439T>G) in 266 Macedonians and 94 Albanians using the TaqMan allelic discrimination assay. No significant difference in the frequencies of the single nucleotide polymorphisms (SNPs) was observed between these populations. The frequency of the c.521T>C SNP was the lowest (<13.7 and 12.2%, respectively), while the frequencies of all other SNP alleles were above 40.0%. Variant alleles of c.1463G>C and c.1086 C>T SNPs were not identified in either ethnic group. The haplotype analysis revealed 20 and 21 different haplotypes in the Macedonian and Albanian population, respectively. The most common haplotype in both ethnic groups, *1J/*1K/*1L, had a frequency of 39.0% and 26.6%, respectively. In both populations, the variant alleles of the functionally significant c.521T>C and c.388A>G SNPs existed in one major haplotype (*15/*16/*17), with a frequency of 8.6 and 2.4% in the Macedonian and Albanian subjects, respectively. In conclusion, sequence variations of the SLCO1B1 gene in the studied populations occur at high frequencies, which are similar to that of the Caucasian population. Further studies are needed to evaluate the clinical significance of these SNPs and/ or the major SLCO1B1 haplotypes they form for a large number of substrates and for susceptibility to certain diseases.

scholarly journals Organic anion transporter 3 (Oat3/Slc22a8) knockout mice exhibit altered clearance and distribution of penicillin G

2007 ◽  
Vol 293 (4) ◽  
pp. F1332-F1341 ◽  
Author(s):  
Adam L. VanWert ◽  
Rachel M. Bailey ◽  
Douglas H. Sweet
Keyword(s):  
Knockout Mice ◽  
Drug Disposition ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Penicillin G ◽  
Anion Transporter ◽  
Organic Anion Transporter 3

The interaction of renal basolateral organic anion transporter 3 (Oat3) with commonly used pharmacotherapeutics (e.g., NSAIDs, β-lactams, and methotrexate) has been studied extensively in vitro. However, the in vivo role of Oat3 in drug disposition, in the context of other transporters, glomerular filtration, and metabolism, has not been established. Moreover, recent investigations have identified inactive human OAT3 polymorphisms. Therefore, this investigation was designed to elucidate the in vivo role of Oat3 in the disposition of penicillin G and prototypical substrates using an Oat3 knockout mouse model. Oat3 deletion resulted in a doubling of penicillin's half-life ( P < 0.05) and a reduced volume of distribution ( P < 0.01), together yielding a plasma clearance that was one-half ( P < 0.05, males) to one-third ( P < 0.001, females) of that in wild-type mice. Inhibition of Oat3 abolished the differences in penicillin G elimination between genotypes. Hepatic accumulation of penicillin was 2.3 times higher in male knockouts ( P < 0.05) and 3.7 times higher in female knockouts ( P < 0.001). Female knockouts also exhibited impaired estrone-3-sulfate clearance. Oat3 deletion did not impact p-aminohippurate elimination, providing correlative evidence to studies in Oat1 knockout mice that suggest Oat1 governs tubular uptake of p-aminohippurate. Collectively, these findings are the first to indicate that functional Oat3 is necessary for proper elimination of xenobiotic and endogenous compounds in vivo. Thus Oat3 plays a distinct role in determining the efficacy and toxicity of drugs. Dysfunctional human OAT3 polymorphisms or instances of polypharmacy involving OAT3 substrates may result in altered systemic accumulation of β-lactams and other clinically relevant compounds.

scholarly journals Somatic variants for seed and fruit set in grapevine

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Laura Costantini ◽  
Paula Moreno-Sanz ◽  
Chinedu Charles Nwafor ◽  
Silvia Lorenzi ◽  
Annarita Marrano ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Fruit Set ◽  
Climatic Factors ◽  
Embryo Sac ◽  
Wine Industry ◽  
Nucleotide Polymorphisms ◽  
Wine Quality ◽  
Single Nucleotide ◽  
Germplasm Collections

Abstract Background Grapevine reproductive development has direct implications on yield. It also impacts on berry and wine quality by affecting traits like seedlessness, berry and bunch size, cluster compactness and berry skin to pulp ratio. Seasonal fluctuations in yield, fruit composition and wine attributes, which are largely driven by climatic factors, are major challenges for worldwide table grape and wine industry. Accordingly, a better understanding of reproductive processes such as gamete development, fertilization, seed and fruit set is of paramount relevance for managing yield and quality. With the aim of providing new insights into this field, we searched for clones with contrasting seed content in two germplasm collections. Results We identified eight variant pairs that seemingly differ only in seed-related characteristics while showing identical genotype when tested with the GrapeReSeq_Illumina_20K_SNP_chip and several microsatellites. We performed multi-year observations on seed and fruit set deriving from different pollination treatments, with special emphasis on the pair composed by Sangiovese and its seedless variant locally named Corinto Nero. The pollen of Corinto Nero failed to germinate in vitro and gave poor berry set when used to pollinate other varieties. Most berries from both open- and cross-pollinated Corinto Nero inflorescences did not contain seeds. The genetic analysis of seedlings derived from occasional Corinto Nero normal seeds revealed that the few Corinto Nero functional gametes are mostly unreduced. Moreover, three genotypes, including Sangiovese and Corinto Nero, were unexpectedly found to develop fruits without pollen contribution and occasionally showed normal-like seeds. Five missense single nucleotide polymorphisms were identified between Corinto Nero and Sangiovese from transcriptomic data. Conclusions Our observations allowed us to attribute a seedlessness type to some variants for which it was not documented in the literature. Interestingly, the VvAGL11 mutation responsible for Sultanina stenospermocarpy was also discovered in a seedless mutant of Gouais Blanc. We suggest that Corinto Nero parthenocarpy is driven by pollen and/or embryo sac defects, and both events likely arise from meiotic anomalies. The single nucleotide polymorphisms identified between Sangiovese and Corinto Nero are suitable for testing as traceability markers for propagated material and as functional candidates for the seedless phenotype.

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