Suppression by protease-activated receptor-2 activation of gastric acid secretion in rats

Suppression by protease-activated receptor-2 activation of gastric acid secretion in rats
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DOI:
10.1016/s0014-2999(02)01892-7
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发表时间:
2002-06-28
影响因子:
5
通讯作者:
Kawabata, A
Kawabata, A
中科院分区:
医学2区
文献类型:
--
作者:
Nishikawa, H;Kawai, K;Kawabata, A

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蛋白酶激活受体 2 (PAR-2)(一种由胰蛋白酶/类胰蛋白酶激活的受体)的激活可诱导神经介导的胃粘液分泌,并伴有粘膜细胞保护。在本研究中,我们研究了 PAR-2 是否可以调节大鼠的胃酸分泌。在胃粘膜和平滑肌中检测到 PAR-2 和 PAR-1 的信使 RNA。当静脉注射时,PAR-2 激活肽 SLIGRL-NH2(而非无活性对照肽)强烈抑制幽门结扎大鼠对卡巴胆碱、五肽胃泌素或 2-脱氧-D-葡萄糖的胃酸分泌。 PAR-2 介导的酸分泌抑制对环氧合酶抑制或辣椒素对感觉神经元的消融具有抵抗力。我们的结果提供了新的证据,表明除了刺激神经介导的粘液分泌之外,PAR-2 的激活还可以独立于前列腺素生成或感觉神经元抑制胃酸分泌。 PAR-2 的这些双重作用将导致胃粘膜细胞保护。 (C) 2002 Elsevier Science B.V. 保留所有权利。
Activation of protease-activated receptor-2 (PAR-2), a receptor activated by trypsin/tryptase, induces neurally mediated gastric mucus secretion accompanied by mucosal cytoprotection. In the present study, we investigated whether PAR-2 could modulate gastric acid secretion in rats. Messenger RNAs for PAR-2 and PAR-1 were detected in the gastric mucosa and smooth muscle. The PAR-2-activating peptide SLIGRL-NH2, but not the inactive control peptide, when administered i.v., strongly suppressed gastric acid secretion in response to carbachol, pentagastrin or 2-deoxy-D-glucose in the rats with a pylorus ligation. The PAR-2-mediated suppression of acid secretion was resistant to cyclooxygenase inhibition or ablation of sensory neurons by capsaicin. Our results provide novel evidence that in addition to stimulating neurally mediated mucus secretion, activation of PAR-2 suppresses gastric acid secretion independently of prostanoid production or sensory neurons. These dual actions of PAR-2 would result in gastric mucosal cytoprotection. (C) 2002 Elsevier Science B.V. All rights reserved.