Edvinsson L, Jansen Olesen I, Kingman T A, McCulloch J, Uddman R
Department of Internal Medicine, University Hospital, Lund, Sweden.
Cephalalgia. 1995 Oct;15(5):373-83. doi: 10.1046/j.1468-2982.1995.1505373.x.
The functional role of the trigeminal system has been addressed in experiments on the cortical surface of alpha-chloralose anaesthetized cats. Application of calcitonin gene-related peptide (CGRP) caused a concentration-dependent increase in arteriolar calibre by 38 +/- 5% (n = 8) with an IC50 of 2 nM. Cerebral veins did not relax upon CGRP administration (n = 12). Substance P (SP) was less potent but showed dilatation of both arterioles (21 +/- 4%) and veins (16 +/- 4%). The cerebrovascular trigeminal system was investigated after chronic (14 days) surgical lesion of the trigeminal nerve with the concomitant disappearance of perivascular CGRP/SP immunoreactive nerves. The cortical arteriolar responses to subarachnoid microinjections of acidic (pH 6.8) and basic CSF (pH 7.6) as well as noradrenaline (10(-4) M), neuropeptide Y (10(-7) M), prostaglandin F2x (10(-6 M), barium chloride (10(-4) M), and autologous blood (5 microl) were examined in anaesthetized cats with lesions of the trigeminal nerve, and were compared with their effects in sham-operated animals. The magnitude of the vasodilator and vasoconstrictor responses to these agents was unaffected by trigeminal lesions. However, duration of the vasoconstriction produced by basic CSF, but not the vasodilitation to acidic CSF, was markedly prolonged by trigeminal lesions (from 0.8 +/- 0.1 min to 2.2 +/- 0.3 min, p < 0.01). Also, the vasoconstrictor responses to noradrenaline, prostaglandin F2x, barium chloride, and autologous blood were significantly prolonged, while the maximum contractile effect to each agent was similar in lesioned as in sham-operated controls. The effects of CGRP, SP, and neurokinin A (NKA) have been examined on isolated cerebral arteries in vitro. Different CGRP analogues induced a strong relaxation with no difference in Imax (85-96%) or pD2 values (8.65 - 9.12). NKA induced a stronger relaxation than SP (Imax: 33% and 13%, respectively). SP was more potent than NKA (pD2:8.7 and 7.7, respectively). Capsaicin, a substance which selectively causes the release of stored sensory neuropeptides (CGRP, SP, NKA), caused in vitro relaxation of precontracted arteries. This relaxation was not affected by the neurokinin blocker spantide, but shifted towards higher capsaicin concentrations by the CGRP antagonist (CGRP 8-37. Thus, in this preparation CGRP rather than a neurokinin (SP/NKA) is responsible for the capsaicin-induced dilatations.
在对α-氯醛糖麻醉猫的皮质表面进行的实验中，研究了三叉神经系统的功能作用。应用降钙素基因相关肽（CGRP）可使小动脉口径呈浓度依赖性增加38±5%（n = 8），半数抑制浓度（IC50）为2 nM。给予CGRP后，脑静脉未出现舒张（n = 12）。P物质（SP）的作用较弱，但可使小动脉（21±4%）和静脉（16±4%）均出现扩张。在三叉神经进行慢性（14天）手术损伤且血管周围CGRP/SP免疫反应性神经随之消失后，对脑血管三叉神经系统进行了研究。在麻醉的三叉神经损伤猫中，检测了皮质小动脉对蛛网膜下腔微量注射酸性（pH 6.8）和碱性脑脊液（pH 7.6）以及去甲肾上腺素（10⁻⁴ M）、神经肽Y（10⁻⁷ M）、前列腺素F2α（10⁻⁶ M）、氯化钡（10⁻⁴ M）和自体血（5 μl）的反应，并与假手术动物的反应进行了比较。三叉神经损伤未影响这些药物引起的血管舒张和收缩反应的幅度。然而，碱性脑脊液引起的血管收缩持续时间（而非酸性脑脊液引起的血管舒张持续时间）在三叉神经损伤后明显延长（从0.8±0.1分钟延长至2.2±0.3分钟，p < 0.01）。此外，去甲肾上腺素、前列腺素F2α、氯化钡和自体血引起的血管收缩反应也明显延长，而损伤组和假手术对照组对每种药物的最大收缩效应相似。已在体外对分离的脑动脉研究了CGRP、SP和神经激肽A（NKA）的作用。不同的CGRP类似物均引起强烈舒张，最大舒张幅度（Imax）（85 - 96%）或亲和力常数（pD2值）（8.65 - 9.12）无差异。NKA引起的舒张比SP更强（Imax分别为33%和13%）。SP比NKA更有效（pD2分别为8.7和7.7）。辣椒素是一种能选择性促使储存的感觉神经肽（CGRP、SP、NKA）释放的物质，可使预收缩的动脉在体外舒张。这种舒张不受神经激肽阻断剂spantide的影响，但CGRP拮抗剂（CGRP 8 - 37）可使舒张向更高的辣椒素浓度偏移。因此，在该制剂中，CGRP而非神经激肽（SP/NKA）是辣椒素诱导舒张的原因。
