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Activation of Meningeal 5‐HT 2B Receptors: An Early Step in the Generation of Migraine Headache?
Author(s) -
Schmuck Karin,
Ullmer Christoph,
Kalkman Hans O.,
Probst Alphonse,
Lübbert Hermann
Publication year - 1996
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1996.tb01583.x
Subject(s) - receptor , migraine , 5 ht2c receptor , serotonin , 5 ht receptor , pharmacology , medicine , endocrinology , biology , chemistry
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‐HT 2B or 5‐HT 2C . 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‐HT 2B receptor. Furthermore, the potency of drugs used in migraine prophylaxis to stimulate or inhibit 5‐HT 2B or 5‐HT 2C 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‐HT 2B ( P = 0.001) than for the 5‐HT 2C 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‐HT 1Dβ , 5‐HT 2A , 5‐HT 2B , 5‐HT 4 and 5‐HT 7 mRNAs. Only trace amounts of 5‐HT 2C receptor mRNA were found. With organ bath experiments we showed that the 5‐HT 2B receptor stimulated the relaxation of the pig cerebral artery via the release of nitric oxide. Our data support the hypothesis that 5‐HT 2B receptors located on endothelial cells of meningeal blood vessels trigger migraine headache through the formation of nitric oxide.