Neurotransmitter And Bioactiveamines Regulate Organic Anion Transport By Organic Anion Transporter On MDCK Cellmembrane

Kidney plays an important role in drug elimination and in sequence,pharmacokinetics. Renal reabsorption and secretion is the main functionalprocess of renal tubule. Madin-Darby canine kidney（MDCK）cell linewas originated from the kidney distal convoluted tubule epithelial (DCT)cells. The MDCK cell monolayer is a ideal in vitro model for drugtransport in kidney. We have taken our attention to the function oftransport of DCT cells recently. PBD, an organic acid and a substrate oforganic anion transporters (OATs) was chosen as the model drug aim tofigure the regulation of OATs by nerves (neurotransmitters) or endocrinesystem on MDCK cell monolayer.Methods: the methods were followed below.(1)To establish MDCKmonolayer in order to figure out the function of transport of PBD, thendiscuss the modes of absorption and secretion of PBD;(2)To simulate theinternal environment, the regulation from neurotransmitters of MDCK monolayer will be observed and analyzed. The observed factors includesorts of neurotransmitters which simulate the internal environment, suchas Adrenaline hydrochloride, Noradrenaline bitartrate, Isoprenalinehydrochloride,5-HT, Histamine, DA, and the DA competitive inhibitorHaloperidol, respectively.Results:(1) PBD can be transported across the MDCK cellmonolayer, and the amount of secretion was as1.5folds high thanabsorption.(2) Adrenaline hydrochloride can inhibitor both the process ofabsorption and secretion but at the different extents. It can be inferred theways of transport mediated diverse subtypes.(3) The PBD secretion canbe decreased with the effect of5-HT and absorption, but there are nosimilar results about absorption. It can be suggested that absorption andsecretion not relay on the same transport protein.(4) Haloperidol caneffectively inhibit the secretion of PBD from MDCK cell monolayerincubated with DA.(5) At last, we observed the secretion of PBD wasmarkedly decreased by Adrenaline hydrochloride,5-HT and DA of whichcan regulate the protein phosphorylation.Conclusion(1)The renal DCT epithelial cell has the function both of secretionand reabsorption.(2)The transport of OAcan be mediated by organic anion and can beregulated by phosphorylation. (3)The MDCK cell monolayer is the ideal method in the research ofdrug transportation cross DCT cells and its mechanisms.