title: Transport of somatostatin and substance P by human P-glycoprotein.
abstract: P-glycoprotein is an efflux pump for a broad spectrum of hydrophobic agents. We found that bioactive peptides including somatostatin and substance P inhibit ATP-dependent vincristine binding to P-glycoprotein-overexpressing K562/ADM membrane vesicles. Some of these bioactive peptides including somatostatin stimulate basal ATPase activity of P-glycoprotein; in contrast, other peptides including substance P inhibit it. The K562/ADM membrane vesicles showed an ATP-dependent, osmotically sensitive uptake of somatostatin and substance P, which was inhibited by valspodar, an inhibitor of P-glycoprotein. These findings suggested that certain bioactive peptides such as somatostatin and substance P directly interact with human P-glycoprotein as endogenous substrates for P-glycoprotein-mediated transport.
authors.affiliation: Novartis Pharma K.K., Tsukuba Research Institute, Okubo 8, Tsukuba, Ibaraki 300-2611, Japan. noriko.uchiyama@pharma.novartis.com
authors.forename: Noriko
authors.initials: N
authors.lastname: Uchiyama-Kokubu
authors.forename: Mikihiko
authors.initials: M
authors.lastname: Naito
authors.forename: Motowo
authors.initials: M
authors.lastname: Nakajima
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuruo
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D000595:Amino Acid Sequence; D006801:Humans; D021381:Protein Transport; D013004:Somatostatin / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D013373:Substance P; D013004:Somatostatin