Characterization of gastrointestinal absorption of digoxin involving influx and efflux transporter in rats: application of mdr1a knockout (-/-) rats into absorption study of multiple transporter substrate.

1. This study was aimed to characterize gastrointestinal absorption of digoxin using wild-type (WT) and multidrug resistance protein 1a [mdr1a; P-glycoprotein (P-gp)] knockout (-/-) rats. 2. In WT rats, the area under the plasma concentration-time curve (AUC) of oral digoxin increased after oral pretreatment with quinidine at 30 mg/kg compared with non-treatment, but the increasing ratio tended to decrease at a high dose of 100 mg/kg. In mdr1a (-/-) rats, however, quinidine pretreatment caused a dose-dependent decrease in the AUC. 3. Quinidine pretreatment did not alter the hepatic availability of digoxin, indicating that the changes in the digoxin AUC were attributable to inhibition of the absorption process by quinidine; i.e. inhibition of influx by quinidine in mdr1a (-/-) rats and inhibition of efflux and influx by quinidine in WT rats. 4. An in situ rat intestinal closed loop study using naringin implied that organic anion transporting peptide (Oatp) 1a5 may be a responsible transporter in the absorption of digoxin. 5. These findings imply that the rat absorption behavior of digoxin is possibly governed by Oatp1a5-mediated influx and P-gp-mediated efflux. The mdr1a (-/-) rat is therefore a useful in vivo tool to investigate drug absorption associated with multiple transporters including P-gp.

Nine acetylenic alcohols isolated from the Okinawan marine sponge of the genus Petrosia (Strongylophora).

Nine new acetylenic alcohols 1-9 were isolated from a marine sponge belonging to the genus Petrosia (Strongylophora). The structures were elucidated mainly based on the analysis of one-and two-dimensional NMR spectral data. To determine the position of the central double bonds in 1-8, each compound was cleaved with OsO(4) and HIO(4), and the resulting aldehyde was converted to the corresponding 2,4-dinitrophenylhydrazone. Analysis of the high-resolution mass and (13)C NMR spectral data of each 2,4-dinitrophenylhydrazone clarified the position of the central double bonds in 1-8.

Structural and physiological studies on the storage beta-polyglucan of haptophyte Pleurochrysis haptonemofera.

The storage beta-polyglucan and catabolic enzyme activities of the haptophyte Pleurochrysis haptonemofera were characterized. The storage beta-polyglucan was prepared by the dimethylsulfoxide-extraction method. (13)C- and (1)H-NMR spectroscopy revealed that the polyglucan consists of beta-(1-->3)- and beta-(1-->6)-linked glucose polymers, with a beta-(1-->6)- to beta-(1-->3)-linkage ratio of 1.5. Gel permeation chromatography showed that the molecular weight of the polyglucan is 1.1-8.4 x 10(4) Da, with a peak at 3.4 x 10(4) Da. The degree of polymerization, which was estimated from the amounts of total carbohydrate and reduced ends, was 203, corresponding to 3.3 x 10(4) Da. A method for measurement of the beta-polyglucan in a small amount of liquid culture involving a mixture of beta-glucanases, Westase, was established. The beta-polyglucan was localized in the soluble fraction of cells. The amount of beta-polyglucan per cell increased at the stationary phase under continuous illumination and decreased in the dark, like those of storage alpha-polyglucans, starch of green algae and glycogen of cyanobacteria. The activities of beta-1,3- and beta-1,6-glucanases involved in the degradation of the storage beta-polyglucan were assayed in vitro, both being optimal at pH 5.0. The beta-1,3-glucanase activity, which was detected on active staining after native polyacrylamide gel electrophoresis, was partially purified by ammonium sulfate precipitation and anion exchange chromatography.

Isolation of peridinin-related norcarotenoids with cell growth-inhibitory activity from the cultured dinoflagellate of Symbiodinium sp., a symbiont of the Okinawan soft coral Clavularia viridis, and analysis of fatty acids of the dinoflagellate.

Two norcarotenoids, 1 and 2, related to peridinin (3) were isolated from the cultured dinoflagellate of the genus Symbiodinium, a symbiont of the Okinawan soft coral Clavularia viridis, which contains in abundance antitumor marine prostanoids such as clavulones. The structures of 1 and 2 were elucidated on the basis of spectroscopic analysis. These compounds showed significant growth-inhibitory activity in vitro toward cancer cells. Analysis of fatty acids of the dinoflagellate was also carried out, suggesting that the marine prostanoids are produced by the host soft coral itself.