天門冬酸及NMDA在鼠胃生理角色之研究

The Physiological Roles of L-Aspartic Acid and NMDA on Rat Stomach

李憶菁(Yih-Jing Lee)

指導教授 ： 蔡麗雪

臺北醫學大學/醫學院/醫學科學研究所/碩士(1995年)

摘要

天門冬酸（L-Aspartic acid）是哺乳類動物體內興奮性胺基酸（excitatory amino acids）之一種。本研究的目的即是要研究天門冬酸及NMDA (N-methyl-D-aspartate)對於胃酸分泌，其信號傳訊系統及胃黏膜血流等方面的影響。結果顯示，天門冬酸可以抑制由histamine誘發的胃酸分泌作用，且是經由興奮性胺基酸之NMDA受體（receptor）來控制；而NMDA也可以抑制由oxotremorine, histamine，以及pentagastrin誘發的胃酸分泌作用，且被NMDA受體的拮抗劑（antagonist）AP-5 (2-amino-5-phosphovaleric acid)及CPP所抑制。在其訊號傳遞方面，我們將鼠胃分成肌肉層及黏膜層（包括 submucosal connective tissues）以各種作用劑或拮抗劑處理，發現天門冬酸及NMDA可以使胃黏膜層細胞內cGMP含量上升，而且此cGMP 增加的現象可以被NO synthase抑制劑（nitric oxide synthase inhibitor）L-NNA（N-nitro-L-arginine）阻斷，同時histamine作用黏膜層細胞可以使cAMP增加，而加入NMDA時cAMP並無增加，但是cGMP隨劑量依存性（dose-dependence）而增加。另一方面，天門冬酸對於由histamine誘發的胃黏膜血流上升的現象有抑制作用。此項抑制血流上升的現象，是經由NMDA受體來作用，而且受NO及交感神經之α1受體調控。 　綜合以上結果，天門冬酸在胃部的作用是抑制histamine誘發之酸分泌，而NMDA則可以抑制oxotremorine及pentagastrin誘發之酸分泌作用；且二者對於histamine誘發之胃黏膜血流上升皆有抑制的作用。天門冬酸對於胃酸分泌及胃黏膜血流的調控，可能是經由NMDA受體cGMP-NO路徑，同時其黏膜血流的變化也受交感神經之α1受體來調控。

關鍵字

天門冬酸

並列摘要

The excitatory amino acids (EAAs), L-aspartic acid (L-Asp) and N-methy-D-aspartate (NMDA) on gastic acid secretion, signal transduction, and mucosal blood flow were investigated. Perfusion with L-Asp and NMDA did not modify the basal secretion of gastric acid. However, NMDA reduced the oxotremorine-, histamine-, and pentagestrin-stinulated acid secretion, while L-Asp markedly reduced histamine-stimulated acid secretion. These inhibitory effects of L-Asp and NMDA were blocked by AP-5 (2-amino-5-phosphovaleric acid) or CPP, the selective NMDA receptor antagonists. As for signal transduction, we separated rat stomach into two parts, muscle layer and mucosal layer (including submucosal connective tissue), and treated with various agonists and antagonists. It was found that both L-Asp and NMDA increased cGMP content of gastric mucosal cells dose-dependently, and this increasing effect could be blocked by NO synthase inhibitor L-NNA. Histamine evoked cAMP accumulation in gastric mucosal layer, but the cAMP accumultion was abolished by the presence of NMDA. Besides, L-Asp also inhibited the histamine-induced increase on gastric mucosal blood flow. The effet of L-Asp on gastric mucosal microcirculation was studied in the anesthetized rats by Laser Doppler Blood Flowmetry (LDF). L-Asp and NMDA did not significantly reduce both the mucosal and serosal blood flow of stomach. L-Asp and NMDA reduced histamine-induced increase in the gastric mucosal blood flow, but had no influence on serosal blood flow. AP-5 and prazosin reversed the inhibitory effect of L-Asp that suppressed the histamine-induced increase in the gastric blood flow. On the other hand, L-NAME (NG-ninto-L-arginine methyl eater) had no effect to the gastric mucosal blood flow. but reversed the inhibitory phenomenon of L-Asp to histamine-induced increase in the gastric mucosal blood flow. 　These results suggest that L-Asp and NMDA inhibit the histamine-induced acid secretion and increase of gastric mucosal blood flow. Furtherwore, NMDA also inhibits the exotremorine and pentagastrin-induced acid secretion. All these effects may be activated through NMDA receptor and cGMP-NO pathway, while mucosal blood flow is also regulated by adrenergic α1-receptor

並列關鍵字

L-Aspartic Aci