Schmuck K, Ullmer C, Kalkman H O, Probst A, Lubbert H
Preclinical Research, Sandoz Pharma Ltd, 4002 Basel, Switzerland.
Eur J Neurosci. 1996 May;8(5):959-67. doi: 10.1111/j.1460-9568.1996.tb01583.x.
Several pharmaceuticals are frequently dispensed to prevent or reduce the occurrence of migraine attacks. The prophylactic effect of these drugs has been suggested to be caused through blockade of serotonin (5-HT) receptors of type 5-HT2B or 5-HT2C. To elucidate which of these receptors is involved, we first used radioligand binding assays to determine the pharmacological profile of the human and rat-5-HT2B receptor. Furthermore, the potency of drugs used in migraine prophylaxis to stimulate or inhibit 5-HT2B or 5-HT2C receptor-mediated potency of drugs used in migraine prophylaxis to stimulate or inhibit 5-HT2B or 5-HT2C receptor-mediated phosphatidyl inositol hydrolysis was measured. All these drugs were found to block both human receptors. Correlation of the receptor affinities with the potencies used in migraine prophylaxis showed significant correlations, which were better for the 5-HT2B (P = 0.001) than for the 5-HT2C receptor (P = 0.005). Migraine headache is thought to be transmitted by the trigeminal nerve from the meninges and their blood vessels. Using the reverse transcription-polymerase chain reaction, the expression patterns of all cloned G-protein-coupled serotonin receptors were analysed in various human meningeal tissues. All tissues expressed 5-HT1Dbeta, 5-HT2A, 5-HT2B, 5-HT4 and 5-HT7 mRNAs. Only trace amounts of 5-HT2C receptor mRNA were found. With organ bath experiments we showed that the 5-HT2B receptor stimulated the relaxation of the pig cerebral artery via the release of nitric oxide. Our data support the hypothesis that 5-HT2B receptors located on endothelial cells of meningeal blood vessels trigger migraine headache through the formation of nitric oxide.
几种药物常被用于预防或减少偏头痛发作的发生。这些药物的预防作用被认为是通过阻断5-HT2B或5-HT2C型血清素（5-HT）受体而产生的。为了阐明涉及这些受体中的哪一种，我们首先使用放射性配体结合试验来确定人和大鼠5-HT2B受体的药理学特征。此外，还测量了用于偏头痛预防的药物刺激或抑制5-HT2B或5-HT2C受体介导的磷脂酰肌醇水解的效力。发现所有这些药物都能阻断这两种人类受体。受体亲和力与偏头痛预防中使用的效力之间的相关性显示出显著的相关性，5-HT2B受体的相关性更好（P = 0.001），而5-HT2C受体的相关性为（P = 0.005）。偏头痛被认为是由三叉神经从脑膜及其血管传导的。使用逆转录聚合酶链反应，分析了所有克隆的G蛋白偶联血清素受体在各种人类脑膜组织中的表达模式。所有组织均表达5-HT1Dbeta、5-HT2A、5-HT2B、5-HT4和5-HT7 mRNA。仅发现微量的5-HT2C受体mRNA。通过器官浴实验，我们表明5-HT2B受体通过释放一氧化氮刺激猪脑动脉舒张。我们的数据支持这样的假设，即位于脑膜血管内皮细胞上的5-HT2B受体通过一氧化氮的形成引发偏头痛。
