Biomaterial Database

Interaction of pristinamycin IA with P-glycoprotein in human intestinal epithelial cells. 1995

V Phung-Ba, and A Warnery, and D Scherman, and P Wils

UMR133 CNRS/RPR, Rhône-Poulenc Rorer, Centre de Recherche de Vitry-Alfortville, Vitry-sur-Seine, France.

Pristinamycin IA is a cyclo-peptidic macrolactone antibiotic belonging to the streptogramin family. In the present work, the interaction of pristinamycin IA with the multidrug transporter P-glycoprotein was investigated in the differentiated human intestinal epithelial cell line Caco-2. Pristinamycin IA specifically inhibited the efflux of the P-glycoprotein substrate [3H]vinblastine, thus increasing the cellular accumulation of the drug. Pristinamycin IA also reduced by 70% the basolateral to apical secretion of [3H]vinblastine across Caco-2 cell monolayers. The cellular accumulation of [14C]pristinamycin IA was very low and was increased by P-glycoprotein inhibitors (verapamil, chlorpromazine and reserpine). The basolateral to apical transport of [14C]pristinamycin IA was 100-fold higher than apical to basolateral passage. This polarized transport was inhibited by verapamil and by ATP depletion. The results suggest that pristinamycin IA is a substrate for the P-glycoprotein, a finding which may have important consequences for the pharmacokinetics of this drug.

UI	MeSH Term	Description	Entries
D007413	Intestinal Mucosa	Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.	Intestinal Epithelium,Intestinal Glands,Epithelium, Intestinal,Gland, Intestinal,Glands, Intestinal,Intestinal Gland,Mucosa, Intestinal
D012110	Reserpine	An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.	Raunervil,Raupasil,Rausedil,Rausedyl,Serpasil,Serpivite,V-Serp,V Serp
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D002746	Chlorpromazine	The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking DOPAMINE RECEPTORS. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup.	Aminazine,Chlorazine,Chlordelazine,Chlorpromazine Hydrochloride,Contomin,Fenactil,Largactil,Propaphenin,Thorazine,Hydrochloride, Chlorpromazine
D004848	Epithelium	The layers of EPITHELIAL CELLS which cover the inner and outer surfaces of the cutaneous, mucus, and serous tissues and glands of the body.	Mesothelium,Epithelial Tissue,Mesothelial Tissue,Epithelial Tissues,Mesothelial Tissues,Tissue, Epithelial,Tissue, Mesothelial,Tissues, Epithelial,Tissues, Mesothelial
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014700	Verapamil	A calcium channel blocker that is a class IV anti-arrhythmia agent.	Iproveratril,Calan,Cordilox,Dexverapamil,Falicard,Finoptin,Isoptin,Isoptine,Izoptin,Lekoptin,Verapamil Hydrochloride,Hydrochloride, Verapamil
D014747	Vinblastine	Antitumor alkaloid isolated from Vinca rosea. (Merck, 11th ed.)	Vincaleukoblastine,Cellblastin,Lemblastine,Velban,Velbe,Vinblastin Hexal,Vinblastina Lilly,Vinblastine Sulfate,Vinblastinsulfat-Gry,Sulfate, Vinblastine
D014769	Virginiamycin	A cyclic polypeptide antibiotic complex from Streptomyces virginiae, S. loidensis, S. mitakaensis, S. pristina-spiralis, S. ostreogriseus, and others. It consists of 2 major components, VIRGINIAMYCIN FACTOR M1 and virginiamycin Factor S1. It is used to treat infections with gram-positive organisms and as a growth promoter in cattle, swine, and poultry.	Staphylomycin,Antibiotic 899,Eskalin,Founderguard,Stajac,Virgimycine
D020168	ATP Binding Cassette Transporter, Subfamily B, Member 1	A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE).	ATP-Dependent Translocase ABCB1,MDR1 Protein,MDR1B Protein,Multidrug Resistance Protein 1,P-Glycoprotein,P-Glycoprotein 1,ABCB1 Protein,ATP Binding Cassette Transporter, Sub-Family B, Member 1,ATP-Binding Cassette, Sub-Family B, Member 1,CD243 Antigen,PGY-1 Protein,1, P-Glycoprotein,ABCB1, ATP-Dependent Translocase,ATP Dependent Translocase ABCB1,Antigen, CD243,P Glycoprotein,P Glycoprotein 1,PGY 1 Protein,Protein, MDR1B,Translocase ABCB1, ATP-Dependent