title: Spectroscopic detection of endovesiculation by large unilamellar phosphatidylcholine vesicles: effects of chlorpromazine, dibucaine, and safingol.
abstract: Endovesiculation by large unilamellar vesicles (LUVs) induced by cationic amphiphiles is described in this work. A recent procedure to monitor phagocytosis of vesicles by macrophages by determining the amount of the simultaneously internalized water_soluble fluorescent dye HPTS with external quencher was adapted to LUVs (Daleke, D. L.; Hong, K.; Papahadjopoulos, D. Biochim. Biophys. Acta 1990, 1024, 352). Compared to dibucaine and safingol, the local anesthetic chlorpromazine (CPZ) was found to be the most efficient inducer of HPTS-internalization by LUVs. Control experiments using LUVs with entrapped HPTS indicated that the observed dye-internalization does not originate from transient lysis. A strong increase in activity above the critical micelle concentration of CPZ implies the importance of CPZ-micelles for endovesiculation. The significantly less efficient CPZ-induced HPTS-internalization by LUVs with 68 nm compared to 176 nm diameter further diminishes the likelihood of a micelle/bilayer fusion mechanism and supports the presence of 'zipper-type' endovesiculation by LUVs with diameters as small as 68 nm.
authors.affiliation: Department of Chemistry, Georgetown University, Washington, DC 20057, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Tedesco
authors.forename: S
authors.initials: S
authors.lastname: Matile
mesh_terms: D001190:Arylsulfonates / Q000378:metabolism; D002746:Chlorpromazine / Q000494:pharmacology*; D003992:Dibucaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000187:drug effects*; D005456:Fluorescent Dyes / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism*; D011726:Pyridinium Compounds / Q000737:chemistry; D013057:Spectrum Analysis / Q000379:methods; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D001190:Arylsulfonates; D005456:Fluorescent Dyes; D008081:Liposomes; D010713:Phosphatidylcholines; D011726:Pyridinium Compounds; C046466:N,N'-4-xylylenebis(pyridinium); C005047:pyranine; D003992:Dibucaine; D013110:Sphingosine; C005682:safingol; D002746:Chlorpromazine