Gastrointestinal lipolysis and trans-epithelial transport of SMEDDS

Self-microemulsifying drug delivery systems (SMEDDSs) have recently returned to the limelight of academia and industry due to their enormous potential in oral delivery of biomacromolecules. However, information on gastrointestinal lipolysis and trans-epithelial transport of SMEDDS is rare. Aggregation-caused quenching (ACQ) fluorescent probes are utilized to visualize the

Physiological, Pharmacological and Toxicological Implications of Heterodimeric Amino Acid Transporters

The heterodimeric amino acid transporter family is a subfamily of SLC7 solute transporter family which includes 14-transmembrane cationic amino acid transporters and 12-transmembrane heterodimeric amino acid transporters. The members of heterodimeric amino acid transporter family are linked via a disulfide bond to single membrane spanning glycoproteins such as 4F2hc (4F2 heavy chain) and rBAT (related to b0, +-amino acid transporter). Six members are associated with 4F2hc and one is linked to rBAT. Two additional members were identified as ones associated with unknown heavy chains. The members of heterodimeric amino acid transporter family exhibit diverse substrate selectivity and are expressed in variety of tissues. They play variety of physiological roles including epithelial transport of amino acids as well as the roles to provide cells in general with amino acids for cellular nutrition. The dysfunction or hyperfunction of the members of the heterodimeric amino acid transporter family are involved in some diseases and pathologic conditions. The genetic defects of the renal and intestinal transporters b0, +AT/BAT1 (b0, +-type amino acid transporter/b0, +-type amino acid transporter 1) and y+LAT1 (y+L-type amino acid transporter 1) result in the amino aciduria with sever clinical symptoms such as cystinuria and lysin uric protein intolerance, respectively. LAT1 is proposed to be involved in the progression of malignant tumor. xCT (x-C-type transporter) functions to protect cells against oxidative stress, while its over-function may be damaging neurons leading to the exacerbation of brain damage after brain ischemia. Because of broad substrate selectivity, system L transporters such as LAT1 transport amino acid-related compounds including L-Dopa and function as a drug transporter. System L also interacts with some environmental toxins with amino acid-related structure such as cysteine-conjugated methylmercury. Therefore, these transporter would be candidates for drug targets based on new therapeutic strategies.

Vesicular transport as a new paradigm in short-term regulation of transepithelial transport

The vectorial transepithelial transport of water and electrolytes in the renal epithelium is achieved by the polarized distribution of various transport proteins in the apical and basolateral membrane. The short-term regulation of transepithelial transport has been traditionally thought to be mediated by kinetic alterations of transporter without changing the number of transporters. However, a growing body of recent evidence supports the possibility that the stimulus-dependent recycling of transporter-carrying vesicles can alter the abundance of transporters in the plasma membrane in parallel changes in transepithelial transport functions. The abundance of transporters in the plasma membrane is determined by net balance between stimulus-dependent exocytic insertion of transporters into and endocytic retrieval of them from the plasma membrane. The vesicular recycling occurs along the tracts of the actin microfilaments and microtubules with associated motors. This review is to highlight the importance of vesicular transport in the short-term regulatory process of transepithelial transport in the renal epithelium. In the short-term regulation of many other renal transporters, vesicular transport is likely to be also involved. Thus, vesicular transport is now emerged as a wide-spread general regulatory mechanism involved in short-term regulation of renal functions.