Characteristics of Hemichannel-Mediated Substrate Transport in Human Retinal Pigment Epithelial Cells under Deprivation of Extracellular Ca2+
| Autor: | Souhei Maruyama, Ken Ichi Hosoya, Shin Ichi Akanuma, Yoshiyuki Kubo |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pharmacology Lucifer yellow Retina Pharmaceutical Science chemistry.chemical_element Retinal General Medicine Calcium Calcein 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Extracellular medicine Biophysics sense organs Efflux Propidium iodide |
| Zdroj: | Biological and Pharmaceutical Bulletin. 43:1241-1247 |
| ISSN: | 1347-5215 0918-6158 |
| Popis: | Retinal pigment epithelial (RPE) cells form the outer blood-retinal barrier (BRB) and regulate drug/compound exchange between the neural retina and blood in the fenestrated blood vessels of retinal choroid via membrane transporters. Recent studies have elucidated that RPE cells express hemichannels, which are opened by extracellular Ca2+ depletion and accept several drugs/compounds as a transporting substrate. The objective of this study was to elucidate the hemichannel-mediated compound transport properties of the outer BRB. In human RPE cells, namely ARPE-19 cells, time-dependent uptake of fluorescent hemichannel substrates, such as Lucifer Yellow, sulforhodamine-101 (SR-101), and propidium iodide (PI) was promoted under Ca2+-depleted conditions. The uptake of these substrates under Ca2+-depleted conditions exhibited saturable kinetics with a Michaelis-Menten constant (Km) of 87-109 µM. In addition, SR-101 and PI uptake by ARPE-19 cells was dependent of extracellular Ca2+ concentration, and that under Ca2+-depleted conditions was significantly decreased by typical substrates and/or inhibitors for hemichannels. Moreover, Ca2+-depleted conditions promoted the efflux transport of calcein from ARPE-19 cells, and the promoted calcein efflux transport was significantly inhibited by a typical hemichannel inhibitor. These results suggested that hemichannels at the outer BRB were involved in the influx and efflux transport of drugs/compounds. |
| Databáze: | OpenAIRE |
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