Endothelin-1-induced ETA receptor-mediated nociception, hyperalgesia and oedema in the mouse hind-paw:: modulation by simultaneous ETB receptor activation
Endothelin-1-induced ETA receptor-mediated nociception, hyperalgesia and oedema in the mouse hind-paw:: modulation by simultaneous ETB receptor activation
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DOI：
10.1038/sj.bjp.0703154
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发表时间：
2000-03-01
影响因子：
7.3
通讯作者：
Rae, GA
中科院分区：
文献类型：
--
作者：
Piovezan, AP;D'Orléans-Juste, P;Rae, GA
1内皮素-1导致ETA受体介导的增强辣椒素诱导的小鼠伤害性感受。我们已经评估了内皮素-1的这种痛觉过敏作用是否也伴随着其他促炎作用，即伤害感受和水肿，并表征了涉及的内皮素ET受体。后爪注射内皮素-1（0.3-30 pmol）诱导分级的伤害感受性反应（累积舔体时间：载体，20.5 ± 3.3 s;内皮素-1在30 pmol，78.1 ± 9.8 s），主要局限于前15分钟。在30 min时）伤害性感受（溶剂，40.2+/-2.6s;内皮素-1在10 pmol时，98.4+/-5.8 s，但30 pmol无活性），并引起水肿（辣椒素5分钟后爪重量增加：载体，46.3+/-2.3mg;内皮素-1 30 pmol，100.3+/-6.1 mg）。3选择性ETB受体激动剂sarafotoxin S6 c（高达30 pmol）和IRL 1620（高达100 pmol）是无活性的，而内皮素-3（高达30 pmol）仅诱导中度水肿。或A-127722-5（6 μ mol kg（-1）i.v.）阻断内皮素-1（10 pmol）的所有作用，但ETB受体拮抗剂BQ-788（1或10 nmol，i.pl.）5 BQ-788（10 nmol，i.pl.）揭示了30 pmol内皮素-1和内皮素-3的痛觉过敏作用。Sarafotoxin S6c（30 pmol，i.pl.）没有改变内皮素-1诱导的（10 pmol）伤害感受或水肿，但消除了痛觉过敏。6因此，内皮素-1触发小鼠后爪中ETA受体介导的伤害感受、痛觉过敏和水肿。内皮素-1或选择性激动剂同时激活ETB受体可限制肽的痛觉过敏作用，但不限制肽的伤害性或致水肿作用。
1 Endothelin-1 causes ETA receptor-mediated enhancement of capsaicin-induced nociception in mice. We have assessed if this hyperalgesic effect of endothelin-1 is also accompanied by other proinflammatory effects, namely nociception and oedema, and characterized the endothelin ET receptors involved.2 Intraplantar (i.pl.) hind-paw injection of endothelin-1 (0.3-30 pmol) induced graded nociceptive responses (accumulated licking time: vehicle, 20.5+/-3.3 s; endothelin-1 at 30 pmol, 78.1+/-9.8 s), largely confined to the first 15 min. Endothelin-1 (1-10 pmol) potentiated ipsilateral capsaicin-induced (0.1 mu g, i.pl.; at 30 min) nociception (vehicle, 40.2+/-2.6s; endothelin-1 at 10 pmol, 98.4+/-5.8 s, but 30 pmol was inactive), and caused oedema (increase in paw weight 5 min after capsaicin: vehicle, 46.3+/-2.3 mg; endothelin-1 at 30 pmol, 100.3+/-6.1 mg).3 Selective ETB receptor agonists sarafotoxin S6c (up to 30 pmol) and IRL 1620 (up to 100 pmol) were inactive, whereas endothelin-3 (up to 30 pmol) induced only modest oedema.4 ETA receptor antagonists BQ-123 (1 nmol, i.pl.) or A-127722-5 (6 mu mol kg(-1) i.v.) prevented all effects of endothelin-1 (10 pmol), but the ETB receptor antagonist BQ-788 (1 or 10 nmol, i.pl.) was ineffective.5 BQ-788 (10 nmol, i.pl.) unveiled hyperalgesic effects of 30 pmoI endothelin-1 and endothelin-3. Sarafotoxin S6c (30 pmol, i.pl.) did not modify endothelin-1-induced (10 pmol) nociception or oedema, but abolished hyperalgesia.6 Thus, endothelin-1 triggers ETA receptor-mediated nociception, hyperalgesia and oedema in the mouse hind-paw. Simultaneous activation of ETB receptors by endothelin-1 or selective agonists can limit the hyperalgesic, but not the nociceptive or oedematogenic, effects of the peptide.