Jatrorrhizine reduces 5-HT and NE uptake via inhibition of uptake-2 transporters and produces antidepressant-like action in mice

Sun, Siyuan; Zhou, Sisi; Lei, Shaowei; Zhu, Shujie; Wang, Kai; Jiang, Huidi; Zhou, Hui

doi:10.1080/00498254.2018.1542188

Cited by 7 publications

(2 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The amino acids of the OCT1 protein are 82%-96% similar in all species (Burckhardt and Wolff, 2000). Although transporters are expressed at lower levels in the heart than in the liver, several transporters have been reported to be expressed in the human heart, such as OCT3, OCTNs, organic anion transporting polypeptide 2B1, monocarboxylate transporter, and concentrative and equilibrative nucleoside transporters (Zhu et al, 2010;Solbach et al, 2011;Kou et al, 2018;Tzvetkov et al, 2018;Sun et al, 2019). OCT3 was expressed in human cardiomyocytes and vascular endothelial cells (Klaassen and Aleksunes, 2010;Solbach et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Madin-Darby canine kidney (MDCK) cells were obtained from Peking Union Medical College (Beijing, China). The cells were stably transfected with the full-length hOCTN1 cDNA (MDCK-hOCTN1, GenBank accession number NM_003059.2), hOCTN2 cDNA (MDCK-hOCTN2, NM_003060.3), hOCT1 cDNA (MDCK-hOCT1, NM_003057), hOCT3 cDNA (MDCK-hOCT3, NM_021977.3), and hMDR1 cDNA (MDCK-hMDR1), established by our research team (Tu et al, 2013;Sun et al, 2014Sun et al, , 2019Weng et al, 2016). The mRNA expression, protein expression, and function of MDCK-hMDR1 cells were confirmed by qRT-PCR, Western blotting, and uptake study.…”

Section: Cell Culturementioning

confidence: 99%

See 1 more Smart Citation

Organic Cation Transporter 1 and 3 Contribute to the High Accumulation of Dehydrocorydaline in the Heart

Chen

et al. 2020

Drug Metab Dispos

Self Cite

View full text Add to dashboard Cite

Dehydrocorydaline (DHC), one of the main active components of Corydalis yanhusuo, is an important remedy for the treatment of coronary heart disease. Our previous study revealed a higher unbound concentration of DHC in the heart than plasma of mice after oral administration of C. yanhusuo extract or DHC, but the underlying uptake mechanism remains unelucidated. In our investigations, we studied the transport mechanism of DHC in transgenic cells, primary neonatal rat cardiomyocytes, and animal experiments. Using quantitative real-time polymerase chain reaction and Western blotting, we found that uptake transporters expressed in the mouse heart include organic cation transporter 1/3 (OCT1/3) and carnitine/ organic cation transporter 1/2 (OCTN1/2). The accumulation experiments in transfected cells showed that DHC was a substrate of OCT1 and OCT3, with K m of 11.29 6 3.3 and 8.96 6 3.7 mM, respectively, but not a substrate of OCTN1/2. Additionally, a higher efflux level (1.71-fold of MDCK-mock) of DHC was observed in MDCK-MDR1 cells than in MDCK-mock cells. Therefore, DHC is a weak substrate for MDR1. Studies using primary neonatal rat cardiomyocytes showed that OCT1/3 inhibitors (quinidine, decynium-22, and levo-tetrahydropalmatine) prevented the accumulation of DHC, whereas OCTN2 inhibitors (mildronate and l-carnitine) did not affect its accumulation. Moreover, the coadministration of OCT1/3 inhibitors (levo-tetrahydropalmatine, THP) decreased the concentration of DHC in the mouse heart. Based on these findings, DHC may be accumulated partly by OCT1/3 transporters and excreted by MDR1 in the heart. THP could alter the distribution of DHC in the mouse heart. SIGNIFICANCE STATEMENTWe reported the cardiac transport mechanism of dehydrocorydaline, highly distributed to the heart after oral administration of Corydalis yanhusuo extract or dehydrocorydaline only. Dehydrocorydaline (an OCT1/3 and MDR1 substrate) accumulation in primary cardiomyocytes may be related to the transport activity of OCT1/3. This ability, hampered by selective inhibitors (levo-tetrahydropalmatine, an inhibitor of OCT1/3), causes a nearly 40% reduction in exposure of the heart to dehydrocorydaline. These results suggest that OCT1/3 may contribute to the uptake of dehydrocorydaline in the heart.

show abstract