Amann R, Schuligoi R, Lanz I, Donnerer J
Department of Experimental and Clinical Pharmacology, Graz University, Austria.
Eur J Pharmacol. 1995 Jun 12;279(2-3):227-31. doi: 10.1016/0014-2999(95)00169-l.
Histamine is known to cause edema and excitation of small-diameter primary afferent neurons. In the present study we wanted to investigate to which extent afferent neurons participate in histamine-induced edema and, subsequently, determine possible inhibitory effects of a tachykinin NK1 receptor and CGRP receptor antagonist on the histamine response. Intraplantar injection of histamine (0.5 mumol) into the rat hind paw caused a 34% increase of paw volume. In capsaicin-denervated rats, this effect of histamine was nearly abolished. The calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37), but not the tachykinin NK1 receptor antagonist SR140333, caused significant inhibition of the edema response. Further indication that CGRP can promote the histamine action was obtained in capsaicin-denervated rats, where co-injection of CGRP (0.3 pmol) increased the edema response to intraplantar histamine. In additional experiments, plasma protein extravasation in the paw skin was evaluated after close arterial infusion of histamine. Also in these experiments CGRP-(8-37), but not SR140333, significantly reduced the histamine effect. The observation that in the rat hind paw a CGRP receptor antagonist, but not a tachykinin NK1 receptor antagonist, attenuates histamine-induced vascular leakage raises the possibility that in some tissues CGRP receptor antagonists may be superior to tachykinin NK1 receptor antagonists in reducing histamine-induced neurogenic inflammatory responses.
已知组胺可引起水肿并激发小直径初级传入神经元。在本研究中，我们想探究传入神经元在多大程度上参与组胺诱导的水肿，随后确定速激肽NK1受体和降钙素基因相关肽（CGRP）受体拮抗剂对组胺反应可能的抑制作用。向大鼠后爪足底注射组胺（0.5 μmol）导致爪体积增加34%。在辣椒素去神经支配的大鼠中，组胺的这种作用几乎被消除。CGRP受体拮抗剂CGRP -（8 - 37）可显著抑制水肿反应，而速激肽NK1受体拮抗剂SR140333则无此作用。在辣椒素去神经支配的大鼠中共同注射CGRP（0.3 pmol）可增强足底注射组胺引起的水肿反应，这进一步表明CGRP可促进组胺作用。在另外的实验中，在动脉近端注入组胺后评估爪皮肤中的血浆蛋白外渗。同样在这些实验中，CGRP -（8 - 37）可显著降低组胺效应，而SR140333则无此作用。在大鼠后爪中，CGRP受体拮抗剂而非速激肽NK1受体拮抗剂可减轻组胺诱导的血管渗漏，这一观察结果提示在某些组织中，CGRP受体拮抗剂在减轻组胺诱导的神经源性炎症反应方面可能优于速激肽NK1受体拮抗剂。
