Asparagine stimulates piglet intestinal Cl- secretion by a mechanism requiring a submucosal glutamate receptor and nitric oxide.
Amino acids are potential components of oral rehydration solutions for infants, which could combine with glucose to further stimulate intestinal Na+ and water absorption. L-Glutamine, the principal fuel of the intestine, stimulates neutral NaCl absorption and enhances enterocyte DNA synthesis, but is unstable in solution. L-Asparagine (ASN), a more stable amino acid with similar structure to L-glutamine, also stimulates enterocyte proliferation. We determined the effects of ASN on electrolyte transport across piglet jejunum in Ussing chambers. Mucosal but not serosal ASN produced electrogenic Cl- secretion (delta JClnet = -1.8 +/- 0.3 microEq/cm2.hr-1). ASN, when added at 0.1 to 30 mM, increased short-circuit current in a dose-dependent manner with a K1/2 of approximately 5 mM and maximal effect at approximately 10 mM. The stimulation of Cl- secretion by ASN was blocked by pretreatment with serosal tetrodotoxin and bumetanide and was inhibited by preincubation with capsaicin (8-methyl-N-vanillyl-6-nonenamide) or substance P. Inhibition of nitric oxide synthesis with the structural analog of L-arginine, NG-monomethyl-L-arginine, reduced ASN-stimulated secretion by > 70%. Additionally, serosal 6-cyanonitro-quinoxaline 2-3-dione, which is a nonspecific blocker of neural non-N-methyl D-aspartate (NMDA) glutamate receptors, fully inhibited the ASN response (IC50 = 10(-6) M). Inhibition was specific for neurally mediated secretion. We found no inhibition of ASN-stimulated secretion by atropine, ketanserin, indomethacin or L-2-amino-5-phosphonovalerate (specific for NMDA receptors). When compared to ASN, L-glutamate was a weaker stimulator of jejunal Cl- secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Rhoads
J M
JM
Department of Pediatrics, School of Medicine, University of North Carolina, Chapel Hill, USA.
Argenzio
R A
RA
Chen
W
W
Gomez
G G
GG
D000818:Animals; D001216:Asparagine / Q000494:pharmacology*; D002034:Bumetanide / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D017136:Ion Transport; D007583:Jejunum / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D012965:Sodium Chloride / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology; D013552:Swine; D009435:Synaptic Transmission / Q000187:drug effects
D002712:Chlorides; D017470:Receptors, Glutamate; D002034:Bumetanide; D009569:Nitric Oxide; D013373:Substance P; D012965:Sodium Chloride; D001216:Asparagine; D012964:Sodium; D007213:Indomethacin