Tröltzsch Markus, Denekas Thomas, Messlinger Karl
Institute of Physiology & Pathophysiology, University of Erlangen-Nürnberg, Universitätsstr. 17, D-91054 Erlangen, Germany.
Eur J Pharmacol. 2007 May 7;562(1-2):103-10. doi: 10.1016/j.ejphar.2007.01.058. Epub 2007 Feb 8.
In an in vivo preparation of the exposed rat cranial dura mater electrical field stimulation causes increases in blood flow that are mainly due to the vasodilatory effect of calcitonin gene-related peptide (CGRP) released from meningeal afferents. In this preparation the effect of BIBN4096BS, a non-peptide competitive antagonist of CGRP receptors, was examined. Additionally, in an in vitro preparation of the hemisected rat skull the effect of BIBN4096BS on CGRP release stimulated by activation of meningeal afferents was analysed. Injection of BIBN4096BS at cumulative doses of 300 microg/kg and 900 microg/kg caused dose-dependent inhibition of the electrically evoked blood flow increases. The basal blood flow and vital parameters were not significantly changed by any dose. In the hemisected skull BIBN4096BS at 10(-6) M did not alter the CGRP release evoked by depolarizing K(+) concentrations or antidromic electrical stimulation of the trigeminal ganglion. We conclude that neurogenic increases in dural blood flow are reduced by BIBN4096BS without changing basal vascular parameters. This peripheral effect may be important with regard to CGRP receptor inhibition as an antimigraine strategy.
在大鼠硬脑膜暴露的体内实验准备中，电场刺激会使血流量增加，这主要归因于从脑膜传入神经释放的降钙素基因相关肽（CGRP）的血管舒张作用。在此实验准备中，研究了CGRP受体的非肽类竞争性拮抗剂BIBN4096BS的作用。此外，在大鼠颅骨半切的体外实验准备中，分析了BIBN4096BS对脑膜传入神经激活刺激CGRP释放的影响。以300μg/kg和900μg/kg的累积剂量注射BIBN4096BS会导致剂量依赖性抑制电诱发的血流量增加。任何剂量都不会使基础血流量和生命体征参数发生显著变化。在半切颅骨实验中，10⁻⁶M的BIBN4096BS不会改变由去极化钾离子浓度或三叉神经节的逆向电刺激诱发的CGRP释放。我们得出结论，BIBN4096BS可减少硬脑膜血流量的神经源性增加，而不改变基础血管参数。就CGRP受体抑制作为一种抗偏头痛策略而言，这种外周效应可能很重要。
