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Titolo:
EFFECT OF OLSALAZINE ON SODIUM-DEPENDENT BILE-ACID TRANSPORT IN RAT ILEUM
Autore:
CHAWLA A; KARL PI; REICH RN; NARASIMHAN G; MICHAUD GA; FISHER SE; SCHNEIDER BL;
Indirizzi:
CORNELL UNIV,N SHORE UNIV HOSP,COLL MED,DEPT PEDIAT,CTR PEDIAT ILEITIS & COLITIS,RES LAB MANHASSET NY 11030 YALE UNIV,SCH MED,DEPT PEDIAT,DIV PEDIAT GASTROENTEROL HEPATOL NEW HAVEN CT 06510
Titolo Testata:
Digestive diseases and sciences
fascicolo: 5, volume: 40, anno: 1995,
pagine: 943 - 948
SICI:
0163-2116(1995)40:5<943:EOOOSB>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
ULCERATIVE-COLITIS; AZODISAL SODIUM; ILEOSTOMY; EXCRETION; INVITRO;
Keywords:
BILE ACID; ILEUM; OLSALAZINE; 5-AMINOSALICYLIC ACID; DIARRHEA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
20
Recensione:
Indirizzi per estratti:
Citazione:
A. Chawla et al., "EFFECT OF OLSALAZINE ON SODIUM-DEPENDENT BILE-ACID TRANSPORT IN RAT ILEUM", Digestive diseases and sciences, 40(5), 1995, pp. 943-948

Abstract

Olsalazine (OLZ), a relatively new form of 5-aminosalicylic acid (5-ASA), is being used for the treatment of colitis. A major side effect of olsalazine is diarrhea, reported in 12-25% of patients. One suggested mechanism for this side effect is enhanced ileal water and electolyte secretion. We propose that OLZ may also inhibit ileal bile acid (BA)transport, resulting in choleretic diarrhea. This would result in excess BAs reaching the colon, with consequent BA-induced secretory diarrhea. Therefore, we studied the effect of OLZ on rat ileal absorption of taurocholate. BA uptake was determined in rat ileal segments, everted sacs, brush border membrane vesicles (BBMV), and Xenopus laevis oocytes. Segments and everted sacs were treated with 5 mM OLZ for 30 min prior to and throughout 10-min taurocholate (Tc) uptake. Terminal ilealBBMV were used to study the effect of OLZ on sodium-dependent bile acid uptake independent of cellular metabolism. Direct effects on the bile acid carrier were examined using Xenopus laevis oocytes expressing the cloned apical rat ileal BA transporter. In ileal segments 5 mM OLZinhibited 10-min Tc uptake by 69.4 +/- 8.8% (P < 0.01) (N = 10 animals). Increasing concentrations of OLZ resulted in a dose-dependent inhibition of Tc uptake. Ten-minute Tc uptake with 0.5, 1.0, 2.0, 2.5, and5 mM OLZ was inhibited by 13.5, 39.6, 49.7, and 70.5%, respectively. In BBMV, OLZ inhibited 45-sec Tc uptake in a dose-dependent manner butdid not effect Na-dependent L-alanine uptake. Kinetic analysis revealed a noncompetitive inhibition by 2 mM olsalazine. Olsalazine, 5 mM, also inhibited Na-dependent uptake of Tc into oocytes, which expressed the rat ileal sodium-dependent bile acid transporter (8.0 +/- 3.7 vs 2.6 +/- 2.0 pmol/oocyte/hr, P < 0.001). OLZ inhibits sodium-dependent Tc uptake and transmucosal transport in the rat ileum in a dose-dependent manner. This inhibition is relatively specific, noncompetitive, anddoes not require intact cellular mechanisms. This effect of OLZ on ileal function may contribute to the diarrhea frequently observed with this drug.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 20:43:37