Asparagine stimulates piglet intestinal Cl- secretion by a mechanism requiring a submucosal glutamate receptor and nitric oxide.
Asparagine stimulates piglet intestinal Cl- secretion by a mechanism requiring a submucosal glutamate receptor and nitric oxide.
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发表时间：
1995-07
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通讯作者：
J. M. Rhoads;R. Argenzio;W. Chen;G. Gomez
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作者：
J. M. Rhoads;R. Argenzio;W. Chen;G. Gomez
氨基酸是婴儿口服补液液的潜在成分，它可以与葡萄糖结合，进一步刺激肠道Na+和水分的吸收。L-谷氨酰胺是肠道的主要燃料，能刺激中性盐分的吸收，促进肠细胞DNA合成，但在溶液中不稳定。L-天冬酰胺是一种更稳定的氨基酸，与L-谷氨酰胺的结构相似，也能刺激肠细胞的增殖。我们在Ussing小室中测定了ASN对仔猪空肠电解质转运的影响。粘膜ASN而不是浆膜ASN产生电生氯分泌(增量JClnet=-1.8+/-0.3microEq/cm2.hr-1)。当加入0.1-30 mm时，ASN以剂量依赖的方式增加短路电流，K1/2约为5 mm，在约10 mm时效果最好。预先用血清河豚毒素和布美他尼阻断三七总皂苷对氯离子的刺激分泌，用辣椒素(8-甲基-N-香草基-6-农烯酰胺)或P物质预温育可抑制三七总碱对氯离子的分泌。用结构类似的L精氨酸、NG-单甲基L精氨酸抑制三七总皂苷对氯离子的分泌，可使三七总碱的分泌减少70%。此外，神经非N-甲基D-天冬氨酸(NMDA)谷氨酸受体的非特异性阻断剂6-氰基-喹恶啉-2-3-二酮可完全抑制ASN反应(IC50=10(-6)M)。抑制是神经介导的分泌所特有的。阿托品、酮丝氨酸、吲哚美辛和L-2-氨基-5-磷酸戊酸(N-甲基-D-天冬氨酸受体特异性)对三七总皂苷刺激的分泌无抑制作用。与三七总皂甙相比，L-谷氨酸对空肠Cl-分泌的刺激作用较弱。
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)