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首页> 美国卫生研究院文献>British Journal of Pharmacology and Chemotherapy >A calcitonin gene-related peptide (CGRP) antagonist (CGRP8-37) inhibits microvascular responses induced by CGRP and capsaicin in skin.
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A calcitonin gene-related peptide (CGRP) antagonist (CGRP8-37) inhibits microvascular responses induced by CGRP and capsaicin in skin.

机译：降钙素基因相关肽（CGRP）拮抗剂（CGRP8-37）抑制CGRP和辣椒素在皮肤中诱导的微血管反应。

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摘要

1. The effect of the calcitonin gene-related peptide (CGRP) antagonist CGRP8-37 on responses to CGRP and other mediators was investigated in rabbit dorsal skin. 2. Blood flow changes at intradermally-injected sites were measured by a multiple site 133xenon clearance technique. CGRP8-37 had little effect on blood flow at doses up to 0.3 nmol/site, when injected alone, although a significant increase in blood flow was observed at the highest dose tested (1 nmol/site). 3. CGRP8-37 dose-dependently inhibited the increased blood flow induced by human alpha CGRP and human beta CGRP, but had no effect on equivalent vasodilator responses induced by vasoactive intestinal peptide (VIP) and prostaglandin E1 (PGE1). CGRP8-37 showed a preferential ability to inhibit alpha CGRP (IC50 0.04 nmol), when compared with beta CGRP (IC50 greater than or equal to 0.3 nmol). 4. Capsaicin, which selectively activates sensory nerves, caused a dose-dependent increase in blood flow when injected intradermally into rabbit skin. The effects of capsaicin (0.01-0.1 mumol/site) were inhibited by CGRP8-37 (0.3 nmol/site), with a partial but significant attenuation of blood flow induced by the highest dose of capsaicin. 5. Oedema formation, induced by intradermal histamine injection (3 nmol/site), was measured in rabbit skin by the local accumulation of intravenously-injected 125I-labelled albumin. Vasodilator doses of CGRP, PGE1 and capsaicin potentiated, in a synergistic manner, oedema formation induced by histamine. GRP8-37 totally inhibited the potentiating effect of CGRP, partially inhibited the synergistic effect of capsaicin, but did not affect PGE1-induced responses.(ABSTRACT TRUNCATED AT 250 WORDS)
机译：1.在兔背皮肤中研究了降钙素基因相关肽（CGRP）拮抗剂CGRP8-37对CGRP和其他介质的反应。 2.通过多部位133xenon清除技术测量皮内注射部位的血流变化。单独注射时，CGRP8-37在最高0.3 nmol /位点的剂量下对血流几乎没有影响，尽管在最高测试剂量（1 nmol /位点）下观察到血流显着增加。 3. CGRP8-37剂量依赖性地抑制人αCGRP和人βCGRP诱导的血流量增加，但对血管活性肠肽（VIP）和前列腺素E1（PGE1）诱导的等效血管舒张反应无影响。与βCGRP（IC50大于或等于0.3 nmol）相比，CGRP8-37表现出优先抑制αCGRP（IC50为0.04 nmol）的能力。 4.辣椒素可以选择性激活感觉神经，当皮内注射到兔皮中时，会引起血流的剂量依赖性增加。 CGRP8-37（0.3 nmol /位点）抑制了辣椒素（0.01-0.1μmol/位点）的作用，但最高剂量的辣椒素诱导了部分但显着的血流减弱。 5.通过静脉内注射125I标记的白蛋白的局部蓄积来测量皮内组胺注射（3nmol /部位）诱导的水肿形成。 CGRP，PGE1和辣椒素的血管扩张剂剂量以协同方式增强了由组胺引起的水肿形成。 GRP8-37完全抑制CGRP的增强作用，部分抑制辣椒素的协同作用，但不影响PGE1诱导的应答。（摘要截断为250字）

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