Transport Functions of Riboflavin Carriers in the Rat Small Intestine and Colon: Site Difference and Effects of Tricyclic-Type Drugs

Abstract

The present study was aimed at kinetically characterizing the newly found carrier-mediated riboflavin transport system in the rat colon, comparing it with that in the small intestine, and also probing the potential roles of these transport systems in intestinal drug absorption. Riboflavin transport, evaluated by measuring the initial uptake into everted intestinal tissue sacs, was saturable with a Michaelis constant (Km) of 0.13 microM and a maximum transport rate (Jmax) of 0.74 pmol/min/100 mg wet tissue weight (wtw) in the colon. Both the Km and the Jmax were smaller than those (0.57 microM and 4.26 pmol/min/100 mg wtw, respectively) in the small intestine, suggesting that the transport system in the colon has a higher affinity to substrates and a smaller transport capacity than its counterpart in the small intestine. The carrier-mediated riboflavin transport in the colon, similarly to that in the small intestine, was Na+-dependent and inhibited by lumiflavin, a riboflavin analogue with an isoalloxazine ring, but not by D-ribose, which forms the side-chain attached to the isoalloxazine ring in riboflavin. To further clarify the substrate specificities of the transport systems, we examined the effects of several drugs with a tricyclic structure similar to isoalloxazine ring on riboflavin transport. Chlorpromazine, a phenothiazine derivative, was found to inhibit riboflavin transport in both the small intestine and the colon. Methylene blue also was found to be a potent inhibitor in both sites. These results suggest that some tricyclic-type drugs could interfere with intestinal riboflavin absorption by specific carrier-mediated transport systems. These transport systems may play roles in the absorption of tricyclic-type drugs.

Chronic alcohol feeding inhibits physiological and molecular parameters of intestinal and renal riboflavin transport

“…Not only RF transport in the small intestine (site of absorption of dietary RF) is inhibited by chronic exposure to ethanol, but also transport of the vitamin in the colon (the site of absorption of the bacterially synthesized RF) (12,34,39) is (Table 1) and normalized relative to rat ␤-actin. Data are means Ϯ SE of 4 separate samples from 4 rats.…”

“…Previous studies have shown that the normal microflora of the large intestine synthesizes RF (11,31) and that mammalian colonocytes have an efficient carrier-mediated mechanism for RF uptake via RF transporter (39). Therefore, we examined the effect of chronic alcohol feeding on the initial rate of carriermediated RF (24 nM) uptake by rat colon using colonic sheets.…”

Acrodermatitis enteropathica and other nutritional diseases of the folds (intertriginous areas)

“…8,23 Other causes of riboflavin deficiency include hypothyroidism, borate ingestion, phototherapy, and treatment with chlorpromazine, probenicid, and tricyclic antidepressants. 8,24 Phototherapy, similar to light exposure, results in degradation of riboflavin. Borate induces deficiency through displacement from its binding sites, increased urine losses, and inhibition of riboflavin-containing enzymes.…”

Kinetic Characterization of Carrier-Mediated Transport Systems for D-Glucose and Taurocholate in the Everted Sacs of the Rat Colon

“…Values represent computer-fitted parameters: J max , maximum uptake rate; K m , Michaelis constant; a) data from Yuasa et al 6) ; b) Tomei et al 2) cholate transport in the colon was also found to be Na ϩ -dependent in our preceding study, 3) the trace level of ASBT might be functionally modulated in the colon in a different manner to that in the small intestine, or an unidentified ASBT isoform or some other class of carrier might be responsible for taurocholate transport in the colon, like the above speculation about the D-glucose carrier.…”