title: Changes in absorption and excretion of rhodamine 123 by sodium nitroprusside.
abstract: Nitric oxide (NO) donors increase the permeability of water-soluble compounds with neither loss of cell viability nor lactate dehydrogenase release, but the involved mechanism is not fully understood. In this study, we focused on permeation via the transcellular route and P-glycoprotein, which is a typical ABC transporter. We examined the effect of sodium nitroprusside (SNP), which is an NO donor, on the membrane permeation of rhodamine 123 (Rho123), a representative P-gp substrate, and the change in expression level of ileal P-gp. We used an in situ closed loop method in rat ileum to study changes in the permeation of Rho123. The effects of SNP (1 and 10mg/kg) on the mdr-1a mRNA and P-gp protein expression levels were examined by real-time RT-PCR and Western blotting, respectively. The absorption and excretion of Rho123 were significantly increased in an SNP dose-dependent manner when compared with those with no addition, but no changes in protein expression level of P-gp in ileal BBM were observed by SNP administration. The relative activity of P-gp was not changed by SNP administration. On the other hand, the expression level of mdr-1a mRNA was induced by SNP administration. We indicated that SNP could increase the mucosal permeation of Rho123 via the transcellular route without an influence on P-gp, and we showed that this effect is temporary. SNP has no influence on P-gp function and protein expression level in the short term, but they may change in the long term.
authors.affiliation: Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo 192-0392, Japan. takizawa@toyaku.ac.jp
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takizawa
authors.forename: Takuya
authors.initials: T
authors.lastname: Kitazato
authors.forename: Haruka
authors.initials: H
authors.lastname: Ishizaka
authors.forename: Naomi
authors.initials: N
authors.lastname: Kamiya
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Ito
authors.forename: Hisanao
authors.initials: H
authors.lastname: Kishimoto
authors.forename: Mikio
authors.initials: M
authors.lastname: Tomita
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hayashi
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000042:Absorption; D000818:Animals; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007082:Ileum / Q000378:metabolism; D008297:Male; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D009599:Nitroprusside / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D020112:Rhodamine 123 / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005456:Fluorescent Dyes; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D020112:Rhodamine 123