Biomedical subjects

Ryo Norikura

Publications and source records attributed to Ryo Norikura.

2 recordsLinked to original sources

PubMed2006

Involvement of recognition and interaction of carnitine transporter in the decrease of L-carnitine concentration induced by pivalic acid and valproic acid.

PURPOSE: Prodrugs with pivalic acid and valproic acid decrease L-carnitine concentration in plasma and tissues by urinary excretion of acylcarnitine as pivaloylcarnitine (PC) and valproylcarnitine (VC), respectively. We investigated the role of the Na+/L-carnitine cotransporter in the porcine kidney epithelial cell line, LLC-PK1 for the decrease of L-carnitine concentration. METHODS: The uptake of L-[3H]carnitine, acetyl-L-[3H]carnitine (AC), L-[3H]PC and L-[3H]VC were investigated in LLC-PK1 cells seeded in a 6-well culture plate. RESULTS: L-Carnitine and AC uptake in LLC-PK1 cells exhibited Na+ dependency. The Km values for L-carnitine and AC uptake were 11.0 and 8.18 microM, respectively. These results indicated expression of Na+/ L-carnitine cotransporter in LLC-PK1 cells. PC and VC inhibited Na+/L-carnitine cotransporter in the competitive (Ki = 90.4 microM) and noncompetitive (Ki = 41.6 microM) manners, respectively. PC and VC uptake by Na+/L-carnitine cotransporter were not observed in LLC-PK1 cells. CONCLUSIONS: These data suggested that PC and VC formed in the body could not be reabsorbed in the kidney, resulting in the decrease of L-carnitine concentration. In addition, inhibition of L-carnitine reabsorption by VC with lower Ki value could induce the decrease of L-carnitine concentration. Collectively, the recognition and interaction of Na+/L-carnitine cotransporter are important factors for carnitine homeostasis.

Acetylcarnitine↗

PubMed2003

Separate assessment of intestinal and hepatic first-pass effects using a rat model with double cannulation of the portal and jugular veins.

To separately assess intestinal and hepatic first-pass effects with absorption ratio data, we have established an experimental model of rats double-cannulated into the portal and jugular veins. The model allows us to take blood samples simultaneously from conscious rats that have recovered from surgical damage. Double cannulation did not alter the physiological and hematological conditions. Moreover, the plasma concentration profiles of unchanged drug following oral and intravenous administration in the double-cannulated rats were not different from those of rats single-cannulated into the jugular vein. These results suggest that the model can be useful for separately assessing intestinal and hepatic first-pass effects. We evaluated the first-pass effects in the intestine and the liver separately using this model. S-1452, as a model drug with 94% absorption ratio, was administered intravenously and orally to the double-cannulated rats, and the drug concentrations in the portal and systemic plasma were determined, and the rates of elimination from the intestine and liver were estimated. In the first pass, approximately 26% and 56% of the dose were extracted by the intestine and liver, respectively. This method, in which the animal is not restricted nor under anesthesia, allows us to obtain reliable values of individual first pass effects in the intestine and liver. This method can also be an effective tool for assessing the site and extent of drug-drug interaction on the first-pass effects.

Journal Article↗