Lambrecht N, Burchert M, Respondek M, Müller K M, Peskar B M
Department of Experimental Clinical Medicine, Ruhr-University of Bochum, Germany.
Gastroenterology. 1993 May;104(5):1371-80. doi: 10.1016/0016-5085(93)90345-d.
Capsaicin-sensitive neurons contain various peptides including calcitonin gene-related peptide. This study examines (1) whether calcitonin gene-related peptide is involved in capsaicin-induced gastroprotection and (2) whether nitric oxide and prostaglandin are required for calcitonin gene-related peptide to prevent mucosal injury.
Gastroprotection by capsaicin or calcitonin gene-related peptide against ethanol-induced gross and histological damage was studied after pretreatment with the calcitonin gene-related peptide receptor antagonist, human calcitonin gene-related peptide8-37, anti-calcitonin gene-related peptide antibodies, and NG-nitro-L-arginine.
Protection by capsaicin was dose-dependently (50% inhibitory dose, 305 pmol.kg-1.min-1) antagonized by human calcitonin gene-related peptide8-37 and significantly attenuated by anti-calcitonin gene-related peptide antibodies. NG-nitro-L-arginine dose-dependently inhibited the protective effect of calcitonin gene-related peptide (50% inhibitory dose, 0.9 mg/kg), 3 mg/kg completely blocking protection. L-Arginine reversed the effects of NG-nitro-L-arginine. Protection by calcitonin gene-related peptide was neither associated with increased prostaglandin formation nor inhibited by indomethacin.
The results suggest that calcitonin gene-related peptide is an essential mediator of the protection elicited by stimulation of capsaicin-sensitive neurons and that the protective effect of calcitonin gene-related peptide is lost after blockade of the nitric oxide system but not the prostaglandin system.
对辣椒素敏感的神经元含有多种肽类，包括降钙素基因相关肽。本研究旨在探讨：（1）降钙素基因相关肽是否参与辣椒素诱导的胃保护作用；（2）一氧化氮和前列腺素是否是降钙素基因相关肽预防黏膜损伤所必需的。
在用降钙素基因相关肽受体拮抗剂人降钙素基因相关肽8 - 37、抗降钙素基因相关肽抗体及N - 硝基 - L - 精氨酸预处理后，研究辣椒素或降钙素基因相关肽对乙醇诱导的大体和组织学损伤的胃保护作用。
人降钙素基因相关肽8 - 37剂量依赖性地（半数抑制剂量，305 pmol·kg⁻¹·min⁻¹）拮抗辣椒素的保护作用，抗降钙素基因相关肽抗体显著减弱其保护作用。N - 硝基 - L - 精氨酸剂量依赖性地抑制降钙素基因相关肽的保护作用（半数抑制剂量，0.9 mg/kg），3 mg/kg完全阻断保护作用。L - 精氨酸可逆转N - 硝基 - L - 精氨酸的作用。降钙素基因相关肽的保护作用既不伴有前列腺素生成增加，也不受吲哚美辛抑制。
结果表明，降钙素基因相关肽是刺激对辣椒素敏感的神经元所引发保护作用的重要介质，并且在一氧化氮系统被阻断后，降钙素基因相关肽的保护作用丧失，但前列腺素系统被阻断后其保护作用并未丧失。
