Buckley T L, Brain S D, Jose P J, Williams T J
Department of Applied Pharmacology, National Heart & Lung Institute, London.
Neuroscience. 1992 Jun;48(4):963-8. doi: 10.1016/0306-4522(92)90284-9.
The effect of an anti-calcitonin gene-related peptide (CGRP) antibody on responses induced by the sensory C-fibre neuropeptide, CGRP, and capsaicin, which selectively activates C-fibre nerves, was investigated in rabbit skin. Test agents and antibody were injected intradermally. Local blood flow changes were measured by 133Xenon clearance and oedema formation by [125I]albumin accumulation. Preinjection intradermally with the Fab fragment of a goat anti-human alpha CGRP antibody selectively inhibited increased blood flow induced by CGRP (3 x 10(-12) mol/site) and caused a partial, but significant inhibition of increased blood flow induced by capsaicin (3 x 10(-7) mol/site). Oedema induced by histamine and bradykinin was potentiated by vasodilator doses of CGRP and capsaicin. These potentiating effects were significantly inhibited by pretreatment with anti-CGRP Fab. The Fab fragment was more potent in inhibiting capsaicin-induced responses than the parent IgG. These results suggest that capsaicin releases vasodilator quantities of CGRP in rabbit skin.
在兔皮肤中研究了抗降钙素基因相关肽(CGRP)抗体对感觉C纤维神经肽CGRP和辣椒素(选择性激活C纤维神经)诱导反应的影响。将测试剂和抗体皮内注射。通过133氙清除法测量局部血流变化,通过[125I]白蛋白蓄积测量水肿形成。预先皮内注射山羊抗人α-CGRP抗体的Fab片段可选择性抑制CGRP(3×10^(-12) mol/部位)诱导的血流增加,并对辣椒素(3×10^(-7) mol/部位)诱导的血流增加产生部分但显著的抑制作用。组胺和缓激肽诱导的水肿在使用血管舒张剂量的CGRP和辣椒素时会增强。抗CGRP Fab预处理可显著抑制这些增强作用。Fab片段在抑制辣椒素诱导的反应方面比亲本IgG更有效。这些结果表明,辣椒素在兔皮肤中释放血管舒张量的CGRP。