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Drug–nutrient interactions: inhibition of amino acid intestinal absorption by fluoxetine

Published online by Cambridge University Press:  09 March 2007

Elena Urdaneta ,
Isabel Idoate  and
Jesús Larralde
Elena Urdaneta
Affiliation:
Departamento de Fisiología y Nutrición, Universidad de Navarra, C/Irunlarrea s/n, 31008 Pamplona, Spain
Isabel Idoate
Affiliation:
Departamento de Bioquímica, Hospital Virgen del Camino, C/Irunlarrea no. 4, 31008 Pamplona, Spain
Jesús Larralde*
Affiliation:
Departamento de Fisiología y Nutrición, Universidad de Navarra, C/Irunlarrea s/n, 31008 Pamplona, Spain
*
*Corresponding author: Dr Jésus Larralde, fax +34 48 425649; e-mail [email protected]
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Abstract

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Fluoxetine is one of the most widely used antidepressants and nowadays it is also being used to manage obesity problems. In our laboratory we demonstrated that the drug inhibited sugar absorption (Monteiro et al. 1993). The aim of the present work was to determine the effect of fluoxetine on intestinal leucine absorption. Using a procedure of successive absorptions in vivo the drug diminished amino acid absorption by 30% (P < 0.001). Experiments in vitro in isolated jejunum also revealed a reduction in leucine uptake of 37% (P < 0.001). In both cases fluoxetine only affected mediated transport without altering diffusion. In a preparation enriched in basolateral membrane, fluoxetine inhibited the Na+,K+-ATPase (EC 3.6.1.37) activity (55%; P < 0.001) in a non-competitive manner with an inhibition constant (Ki) value of 0.92 mm. Leucine uptake by brush-border membrane vesicles was diminished by the drug (a reduction of 48% was observed at 30s, P < 0.001); only the apical Na+-dependent transport system of the amino acid was modified and the inhibition was non-competitive. Leucine uptake in the presence of lysine indicated that transporter B was involved. These results suggest that fluoxetine reduces leucine absorption by its action on the basolateral and apical membrane of the enterocyte; the nutritional status of the patients under drug treatment may be affected as neutral amino acid absorption is decreased.

Keywords

FluoxetineDrug-nutrient interactionsIntestinal absorption
Type
General Nutrition
Information
British Journal of Nutrition , Volume 79 , Issue 5 , May 1998 , pp. 439 - 446
Copyright
Copyright © The Nutrition Society 1998

References

Angel, I, Faranger, MA, Sacatten, B & Langer, SZ (1988) Mechanism of anoretic activity of serotonin reuptake inhibitors. British Journal of Pharmacology 93, 11–19.Google Scholar
Barcina, Y, Ilundain, A & Larralde, J (1988) Effect of amoxicillin, cephalexin and tetracycline-HCl on intestinal l-leucine transport in rat in vivo. Drug–Nutrient Interactions 5, 283–288.Google ScholarPubMed
Baumann, S (1996) Pharmacokinetic–pharmacodynamic relationship of the selective serotonin reuptake inhibitors. Clinical Pharmacokinetics 31, 444–469.CrossRefGoogle ScholarPubMed
Blundell, JE & Hill, AJ (1989) Do serotoninergic drugs decrease energy intake by reducing fat or carbohydrate intake? Effect of d-fenfluramine with supplemented weight-increasing diets. Pharmacology, Biochemistry and Behavior 31, 773–778.CrossRefGoogle Scholar
Bradford, BB (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry 72, 248–254.CrossRefGoogle ScholarPubMed
Brandsch, M, Brandsch, R, Prasad, MV, Ganapathy, V, Hopfer, U & Leibach, FH (1995) Identification of a renal cell line that constitutively expresses the kidney-specific high-affinity H+-peptide cotransporter. FASEB Journal 9, 1489–1496.CrossRefGoogle ScholarPubMed
Campa, MJ & Kilberg, MS (1989) Characterization of neutral and cationic amino acid transport in Xenopus oocytes. Journal of Cellular Physiology 141, 645–652.CrossRefGoogle ScholarPubMed
Connolly, VM, Gallagher, A & Kesson, CM (1995) A study of fluoxetine in obese elderly patients with type 2 diabetes. Diabetic Medicine 12, 416–418.CrossRefGoogle ScholarPubMed
Del Castillo, JR & Robinson, JW (1982) Simultaneous preparation of basolateral and brush border membrane vesicles from guinea pig intestinal epithelium and the determination of the orientation of the basolateral membrane vesicles. Biochimica et Biophysica Acta 688, 45–56.CrossRefGoogle Scholar
Dixon, J & Hokin, L (1980) The reconstituted (Na+,K+), ATPase is electrogenic. Journal of Biological Chemistry 255, 10681–10686.CrossRefGoogle ScholarPubMed
Fulton, B & McTavish, D (1995) Fluoxetine: an overview of its pharmacodynamic and pharmacokinetic properties and review of its therapeutic efficacy in obsessive-compulsive disorder. CNS Drugs 3, 305–322.CrossRefGoogle Scholar
Ganapathy, V, Brandsch, M & Leibach, FH (1994) Intestinal transport of amino acids and peptides. In Physiology of the Gastrointestinal Tract, p. 1773 [Johnson, LR, editor]. New York: Raven Press.Google Scholar
Gershon, MD, Takaki, M, Tamir, H & Branchek, T (1985) The enteric neural receptor for 5-hydroxytryptamine. Experientia 41, 863–868.CrossRefGoogle ScholarPubMed
Hardcastle, J, Hardcastle, PT, Kelleher, K, Henderson, LS & Fondacaro, JB (1986) Effect of auranofin on absorptive processes in the rat small bowel. Journal of Rheumatology 13, 541–546.Google ScholarPubMed
Harig, JM, Barry, JA, Rajendran, VM, Soergel, KH & Ramaswany, K (1989) d-Glucose and l-leucine transport by human brush-border membrane vesicles. American Journal of Physiology 256, G618–G623.Google Scholar
Hopfer, U, Sigrist-Nelson, K, Perrotto, J & Murer, H (1975) Intestinal sugar transport: studies with isolated plasma membranes. Annals of the New York Academy of Sciences 264, 414–427.CrossRefGoogle ScholarPubMed
Idoate, I, Mendizábal, MV, Urdaneta, E & Larralde, J (1996) Interactions of cephradine and cefaclor with the intestinal absorption of d-galactose. Journal of Pharmacy and Pharmacology 48, 645–650.CrossRefGoogle ScholarPubMed
Jorgensen, JL (1975) Techniques for the study of steroids effects on membraneous (Na+-K+) ATPase. Methods in Enzymology 36, 434–439.CrossRefGoogle Scholar
Jun, FY, Prasad, PD, Leibach, FH & Ganapathy, V (1995) The amino acid transport system y + L induced in Xenopus laevis oocytes by human choriocarcinoma cell (JAR) mRNA is functionally related to the heavy chain of the 4F2 cell surface antigen. Biochemistry 34, 8744–8751.Google Scholar
Luo, S & Li, TS (1990) Food intake and selection pattern of rats treated with dexfenfluramine, fluoxetine and RU 24969. Brain Research Bulletin 24, 729–733.CrossRefGoogle ScholarPubMed
Lerner, J & Larimore, DL (1986) Comparative aspects of the apparent Michaelis constant for neutral amino acid transport in several animal tissues. Comparative Biochemistry and Physiology 84B, 235–241.Google Scholar
McCloud, E, Ma, TY, Grant, KE, Mathis, RK & Said, HM (1996) Uptake of l-carnitine by a human intestinal epithelial cell line, Caco-2. Gastroenterology 111, 1534–1540.CrossRefGoogle ScholarPubMed
Magagnin, S, Bertarn, J & Werner, A (1992) Poly (A)+ RNA from rabbit intestinal mucosa induces b0.+ and y+ amino acid transport activities in Xenopus laevis oocytes. Journal of Biological Chemistry 267, 15384–15388.CrossRefGoogle ScholarPubMed
Mailliard, ME, Stevens, BR & Mann, GE (1995) Amino acid transport by small intestinal, hepatic and pancreatic epithelia. Gastroenterology 108, 888–910.CrossRefGoogle ScholarPubMed
Matthews, JC, Wong, EA, Bender, PK & Webb, KE (1996) Demonstration and characterization of a transport system capable of lysine and leucine absorption that is encoded for in porcine jejunal epithelium by expression of mRNA in Xenopus laevis oocytes. Journal of Animal Sciences 74, 127–137.CrossRefGoogle ScholarPubMed
Mendizábal, MV, Idoate, I, Jordán, J & Larralde, J (1991) Effects of cefroxadine on l-leucine absorption in rat jejunum. Archives International of Physiology, Biochemistry and Biophysics 99, 247–250.Google ScholarPubMed
Mendizábal, MV, Idoate, I & Larralde, J (1990) Effect of cefatrizine and cephaloglycine on l-leucine absorption in rat jejunum. Comparative Biochemistry and Physiology 96C, 317–320.Google Scholar
Monteiro, JB, Jordán, J, Barber, A & Larralde, J (1993) Effect of fluoxetine on the digestion and absorption of carbohydrates. Journal of Clinical Nutrition and Gastroenterology 8, 13–20.Google Scholar
Munck, BG (1989) Amino acid transport across the hen colon: interactions between leucine and lysine. American Journal of Physiology 256, G532–G537.Google ScholarPubMed
Munck, LK (1995) Chloride-dependent amino acid transport in the small intestine: occurrence and significance. Biochimica et Biophysica Acta 1241, 195–213.CrossRefGoogle Scholar
Naftalin, RJ & Curran, PF (1976) Galactose transport in rabbit ileum. Journal of Membrane Biology 16, 257–278.CrossRefGoogle Scholar
O'Kane, M, Wiles, PG & Wales, JK (1994) Fluoxetine in the treatment of obese patients. Diabetes Medica 11, 105–110.CrossRefGoogle Scholar
Pickel, VM, Niremberg, MJ, Chan, J, Moschkovitz, R, Udenfriend, S & Tate, SS (1993) Ultrastructural localization of a neutral and basic amino acid transporter in rat kidney and intestine. Proceedings of the National Academy of Sciences USA 90, 7779–7783.CrossRefGoogle ScholarPubMed
Ponz, F, Ilundain, A & Lluch, M (1979) Methods for successive absorption with intestinal perfusion “in vivo”. Revista Española de Fisiología 35, 97–103.Google ScholarPubMed
Salvador, MT, Rodríguez-Yoldi, MC, Alcalde, AI, Marco, R & Rodríguez-Yoldi, MJ (1996) Serotonin-induced changes in l-leucine transport across rabbit jejunum. Life Sciences 59, 1269–1281.CrossRefGoogle ScholarPubMed
Shirazi-Beechey, SP, Davies, AG, Tebbutt, K & Beechey, R (1990) Preparation and properties of brush-border membrane vesicles from human small intestine. Gastroenterology 98, 676–685.CrossRefGoogle ScholarPubMed
Spring, B, Wurtman, J, Wurtman, R, El-Khoury, A, Goldberg, H, McDeermott, J & Pingitore, R (1995) Efficacies of dexfenfluramine and fluoxetine in preventing weight gain after smoking cessation. American Journal of Clinical Nutrition 62, 1181–1187.CrossRefGoogle ScholarPubMed
Steiner, M, Steinberg, S & Stewart, D (1995) Fluoxetine in the treatment of premenstrual syndrome. New England Journal of Medicine 332, 1529–1534.CrossRefGoogle Scholar
Van Beers, EH, Büller, HA, Grand, RJ, Einerhand, AWC & Dekker, J (1995) Intestinal brush border glycohydrolases: structure function and development. Critical Reviews in Biochemistry and Molecular Biology 30, 197–262.CrossRefGoogle ScholarPubMed
Wise, S (1992) Clinical studies with fluoxetine in obesity. American Journal of Clinical Nutrition 55, 181S–184S.CrossRefGoogle ScholarPubMed
Wong, DT, Bymaster, FP, Horng, JS & Meloy, BB (1975) A new selective inhibitor for uptake into synaptosomes of rat brain: 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropilamine. Journal of Pharmacology and Experimental Therapeutics 193, 804–811.Google Scholar
Wong, DT & Yen, TT (1985) Suppression of appetite and reduction of body weight in normal and obese mice by fluoxetine, a selective inhibitor of serotonin uptake. Federation Proceedings 44, 1162.Google Scholar