Alanine Enhances Jejunal Sodium Absorption in the Presence of Glucose Studies in Piglet Viral Diarrhea

Abstract

ABSTRACT. We measured the response of jejunal sodium (Na) absorption to neutral amino acid (L-alanine) and to dipeptides (L-alanyl-L-alanine, glycylsarcosine) in normal piglets and in piglets with acute viral diarrhea after experimental infection with transmissible gastroenteritis (TGE) virus. In the TGE jejunum villi were blunted, crypts were deepened, and the epithelium was composed of relatively undifferentiated cells with reduced disaccharidase, decreased sodium-potassium-stimulated ATPase, and elevated thymidine kinase activities. The response of Na absorption to a maximal concentration of L-alanine (20 mM) or D-glucose (30 mM) was significantly blunted in TGE jejunum in Ussing chambers. However, the addition of L-alanine together with D-glucose caused a significantly greater increment of Na absorption than either L-alanine or D-glucose alone in control and TGE tissue. The effect of Na absorption of the dipeptide L-alanyl-L-alanine (10 mM), which was rapidly hydrolyzed by control and TGE mucosa, was similar to that of L-alanine (20 mM), while glycylsarcosine, a poorly hydrolyzed dipeptide, did not change net Na absorption in the jejunum. Our data support the concept of separate carrier systems for neutral amino acid and hexose in the crypt-type intestinal epithelium characterizing viral enteritis. We speculate that a sodiumcotransporting amino acid, if added to oral glucose-electrolyte solutions, could benefit oral rehydration therapy in acute viral diarrhea; neither of the dipeptides tested here can be expected to enhance absorption to any greater extent than its constituent amino acids. (Pediatr Res 20: 879-883,1986) Abbreviations Isc, short-circuit current Na, sodium JE:, Na flux from mucosa to serosa Jr;, Na flux from serosa to mucosa JPJ, net Na flux AJZ, increment in net Na flux Na+-K+-ATPase, sodium-potassium-stimulated adenosinetriphosphatase ORT, oral rehydration therapy TGE, transmissible gastroenteritis WHO, World Health Organization Received January 23, 1986; accepted April 30, 1986. Supported by a grant from the Medical Research Council of Canada. J.M.R. was a recipient of a research fellowship from the Canadian Cystic Fibrosis Foundation.All correspondence and requests for reprints should be addressed to J. Richard Hamilton, M.D., Division of Gastroenterology, The Hospital for Sick Children, 555 University Avenue. Toronto, Ontario, Canada M5G 1x8.ORT has greatly improved the outlook for millions of babies aMicted each year with acute enteritis. The current WHO/ UNICEF formulation for oral rehydration has been very effective in restoring the water and electrolyte status of patients with diarrhea, but it does not diminish stool losses (l,2). To accelerate clinical recovery and promote general acceptance of ORT, a solution that actually reduces diarrheal volume would be very desirable.One theoretical approach to improving standard ORT is to incorporate additional nonionic solute in its formulation to promote water and salt absorption in the diseased intestine. To evaluate the pathophysiologica...

Transport of valine across the small intestinal epithelium in pigs fed different valine levels and Bacillus subtilis

“…The epithelial conductance (G) increased with addition of Val (5, 10 and 20 mmol Val/L), which is in accordance with the Isc response to Val addition. The increased G indicates that the Val increased the permeability of the epithelial tissue and confirms other Ussing chamber studies with pig epithelium after adding L‐glutamine (Rhoads, Keku, Bennett, Quinn, & Lecce, ) and L‐alanine (Rhoads, MacLeod, & Hamilton, ). The increased Isc in response to Val is in accordance with earlier observations on the effect of AA's in pig's small intestine (Grøndahl, Munck, & Skadhauge, ; Grøndahl & Skadhauge, ).…”

Pathogenesis of diarrhea

“…The apical membrane of enterocytes is not only provided with symports for sodium/glucose but also for sodium/amino acids. The response of sodium absorption to L-alanine (20 mM) was significantly blunted in intestinal segments exposed to Coronavirus [33]. This conclusion was further strengthened by studies of sodium transport into brush border vesicles, demonstrating a marked inhibition of Na-L-alanine symport in virus enteritis in piglets (Coronavirus) [42] and young rabbits (Rotavirus) [38].…”

“…In the presence of luminal glucose net sodium uptake is turned into secretion, whereas virus evokes no effect in the absence of glucose [24,[31][32][33]. The induced change in sodium transport (glucose present) is in part explained by an attenuated mucosa-to-serosa flux.…”

“…The induced change in sodium transport (glucose present) is in part explained by an attenuated mucosa-to-serosa flux. Surprisingly, the serosa-to-mucosa flux of sodium or chloride ions is larger in the control intestines than in the coronavirus-infected intestines [24,[31][32][33][34][35] despite the fact that morphological measurements often show that the crypts are larger in infected than in control intestines. In line with this, SCCs in control intestines were often found to be greater than in infected intestines in the face of a lower tissue conductance of the infected intestines [32,34].…”

Oral Transforming Growth Factor-α Enhances Jejunal Mucosal Recovery and Electrical Resistance in Piglet Rotavirus Enteritis

“…Furthermore, many more animals with tall jejunal villi (>600 pm) had received TGFa, rather than saline ( p = 0.0094 by Fisher's exact test). Electrical resistance decreases with increasing villus height, but generally increases after viral damage (20). The relationship between epithelial resistance and villus height was explored.…”