Summary
Post-stress metabolism is associated with a large glutamine (Gln) efflux from muscle and an increased Gln utilization by the small intestine. Both appear to be modulated by corticosteroids. The present investigation was performed to better characterize the mechanism of corticoid action on Gln metabolism in an isolated preparation of vascularly perfused rat small intestine. In all perfusions, a synthetic perfusate free from blood components was used with only 0.6 mM Gln and 10 mM glucose as substrates. Irrespective of dexamethasone concentrations in the vascular perfusate (none, 0.25 mg l−1, or 2.5 mg l−1), isolated intestines from normal rats exhibited unchanged extraction rates of Gln (−85±8, −89±10, and −87±16 nmol min−1 g−1) and unchanged production rates of alanine (43±9, 40±7, and 51±5 nmol min−1 g−1) and ammonia (49±15, 45±13, and 54±13 nmol min−1 g−1).
Similarly, when intestines were vascularly perfused 2 or 9 days after dexamethasone injection (0.45 mg kg−1 BW), net Gln uptake also remained unchanged (−88±16 and −84±11 nmol min−1 g−1). There was, however, a shift in nitrogenous products of Gln metabolism from ammonia (−31% and −38%) to alanine (+16% and +64%). Thus, the failure of dexamethasone to increase Gln uptake in the isolated rat intestine may indicate that rather than acting directly on the mucosa, dexamethasone could regulate intestinal Gln consumption in vivo by indirect mechanisms possibly involving extramucosal tissues. Dexamethasone pretreatment may modulate the pattern of nitrogenous products in portal venous blood presented to the liver and thus support enhanced nitrogen loss through ureagenesis by metabolic cooperation between gut and liver.
Similar content being viewed by others
References
Askanazi J, Elwyn DH, Kinney JM, Gump FE, Michelsen CB, Stinchfield MD, Fürst P, Vinnars E, Bergström J (1978) Muscle and plasma amino acids after injury: the role of inactivity. Ann Surg 188:797–803
Bondy PK (1980) The adrenal cortex. In: Bondy PK, Rosenberg LE (eds) The metabolic control and disease. Saunders, Philadelphia, p 1444
Castle SJ, Tucker GT, Woods HF, Underwood JCE, Nicholson CM, Havler ME, Lewis CJ, Flockhart IR, Lloyd-Jones G (1985) Assessment of an in-situ rat intestine preparation with perfused vascular bed for studying the absorption and first-pass metabolism of drugs. J Pharmacol Methods 14:255–274
Dupas JL, Moreau M, Hofmann AF (1985) Polymeric dyes: useful nonabsorbable reference markers for intestinal perfusion studies in animals. J Pharm Sci. 74:328–330
Fox AD, Kripke SA, Berman JM, McGintey RM, Settle RG, Rombeau JL (1988) Dexamethasone administration induces increased glutaminase specific activity in the jejunum and colon. J Surg Res 44:391–396
Geer RJ, Williams PE, Lairmore P, Abumrad NN (1987) Glucagon: an important stimulator of gut and hepatic glutamine metabolism. Surg Forum 38:19–21
Graser TA, Godel HG, Albers S, Földi P, Fürst P (1985) An ultra rapid and sensitive high-performance liquid chromatographic method for determination of tissue and plasma free amino acids. Anal Biochem 151:142–152
Green Cross Corporation (1976) FC-43 Emulsion. The Green Cross Corporation, 1-15-1, Imabashi Higashi-Ku, Osaka, Japan. Technical Information Series No 3
Hartmann F, Vieillard-Baron D, Heinrich R (1984) Isolated perfusion of the small intestine using perfluorotributylamine as artificial oxygen carrier. Adv Exp Med Biol 180:711–720
Häussinger D, Gerok W, Sies H (1984) Hepatic role in pH regulation: role of the intercellular glutamine cycle. Trends Biochem Sci 9:300–302
Haynes RC Jr (1990) Adrenocorticotropic hromone: adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Gilman AG, Rall TW, Nies AS, Taylor P (eds) The pharmacological basis of therapeutics. 8th edn. Pergamon Press, New York, p 1431
Heitmann RN, Bergmann AE (1978) Glutamine metabolism, interorgan transport, and glucogenicity in the sheep. Am J Physiol 234:E197-E203
Kavin H, Levin NW, Stanley MM (1967) Isolated perfused rat small bowel—technique, studies of viability, glucose absorption. J Appl Physiol 22:604–611
Kirk RW (1980) Current veterinary therapy. Vol. VII. Small animal practice. Saunders, Philadelphia
Moore FD (1959) The metabolic care of the surgical patient. Saunders, Philadelphia, pp 55–69
Mühlbacher F, Kapadia CR, Colpoys MF, Smith RJ, Wilmore DW (1984) Effects of glucocorticoids on glutamine metabolism in skeletal muscle. Am J Physiol 247:E75-E83
Newsholme EA, Crabtree B, Ardawi MSM (1985) Glutamine metabolism in lymphocytes: its biochemical physiological and clinical importance. Q J Exp Physiol 70:473–489
Phromphetcharat V, Jackson A, Dass PD, Velbourne TC (1981) Ammonia partitioning between glutamine and urea: interorgan participation in metabolic acidosis. Kidney Int 20:598–605
Plauth M, Hartmann F (1989) The role of the small intestine in intermediary metabolism. Metabolism ofl-glutamine. Prog Pharmacol Clin Pharmacol 7:99–117
Plauth M, Graser TA, Vieillard-Baron D, Bauder D, Fürst P, Hartmann F (1988) Influence of lactulose and paromomycine on the endogenous intestinal ammoniagenesis—correlation of glutamine consumption and ammonia formation. In: Soeters PB, Wilson JHP, Meijer AJ, Holm E (eds) Advances in ammonia metabolism and hepatic encephalopathy. Elsevier, Amsterdam, pp 170–176
Plauth M, Kremer I, Raible A, Stehle P, Fürst P, Hartmann F (1991) Dipeptide metabolism in the isolated perfused rat small intestine. Clin Nutr 10 [Suppl]:26–32
Plauth M, Raible A, Kremer I, Vieillard-Baron D, Bauder-Groß D, Hartmann F (1991) Einfluß von Glucose und Ammonium auf den Glutaminstoffwechsel isoliert perfundierten Rattendünndarm. Infusionstherapie 18:64
Rudermann N (1975) Muscle amino acid metabolism and gluconeogenesis. Annu Rev Med 26:245
Sakai K, Akima M, Hinohara Y, Sasaki M, Niki R (1980) Vascularly perfused rat small intestine: a research model for drug absorption. Jpn J Pharmacol 30:231–241
Souba WW, Wilmore DW (1983) Postoperative alterations of arteriovenous exchange of amino acids across the gastrointestinal tract. Surgery 94:342–350
Souba WW, Smith RJ, Wilmore DW (1985) Glucocorticoids regulate intestinal glutamine consumption. Curr Surg 42:385–388
Souba WW, Smith RJ, Wilmore DW (1985) Effects of glucocorticoids on glutamine metabolism in visceral organs. Metabolism 34:450–456
Tomas FM, Munro HN, Young VR (1979) Effect of glucocorticoid aministration on the rate of muscle breaskdown in vivo in rats, as measured by urinary excretion of 3-methylhistidine. Biochem J 178:139–144
Vaughn GM, Becker RA, Allen JP, Goodwin GW, Pruitt BA, Mason AD (1982) Cortisol and corticotropin in burned patients. J Trauma 22:263–268
Windmueller HG, Spaeth AE (1974) Uptake and metabolism of plasma glutamine by the small intestine. J Biol Chem 249:5070–5079
Windmueller HG, Spaeth AE, Ganote CE (1970) Vascular perfusion of isolated rat gut: norepinephrine and glucocorticoid requirement. Am J Physiol 218:197–204
Author information
Authors and Affiliations
Additional information
Supported by the Deutsche Forschungsgemeinschaft (P1 128/1-1)
Rights and permissions
About this article
Cite this article
Plauth, M., Raible, A., Bauder-Groß, D. et al. Effects of dexamethasone on glutamine metabolism in the isolated vascularly perfused rat small intestine. Res. Exp. Med. 191, 349–357 (1991). https://doi.org/10.1007/BF02576690
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02576690