ACTIVATION OF MENINGEAL 5-HT2B RECEPTORS - AN EARLY STEP IN THE GENERATION OF MIGRAINE HEADACHE

Several pharmaceuticals are frequently dispensed to prevent or reduce the occurrence of migraine attacks. The prophylactic effect of these d rugs 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 re ceptors is involved, we first used radioligand binding assays to deter mine the pharmacological profile of the human and rat 5-HT2B receptor. Furthermore, the potency of drugs used in migraine prophylaxis to sti mulate or inhibit 5-HT2B Or 5-HT2C receptor-mediated phosphatidyl inos itol hydrolysis was measured. All these drugs were found to block both human receptors. Correlation of the receptor affinities with the pote ncies used in migraine prophylaxis showed significant correlations, wh ich were better for the 5-HT2B (P = 0.001) than for the 5-HT2C recepto r (P = 0.005). Migraine headache is thought to be transmitted by the t rigeminal nerve from the meninges and their blood vessels. Using the r everse transcription-polymerase chain reaction, the expression pattern s of all cloned G-protein-coupled serotonin receptors were analysed in various human meningeal tissues. All tissues expressed 5-HT1D beta, 5 -HT2A, 5-HT2B, 5-HT4 and 5-HT7 mRNAs. Only trace amounts of 5-HT2C rec eptor mRNA were found. With organ bath experiments we showed that the 5-HT2B receptor stimulated the relaxation of the pig cerebral artery v ia the release of nitric oxide. Our data support the hypothesis that 5 -HT2B receptors located on endothelial cells of meningeal blood vessel s trigger migraine headache through the formation of nitric oxide.