DIFFERENTIAL EXPRESSION OF SUMATRIPTAN-SENSITIVE 5-HYDROXYTRYPTAMINE RECEPTORS IN HUMAN TRIGEMINAL GANGLIA AND CEREBRAL BLOOD-VESSELS

The efficacy of sumatriptan in migraine relief has been attributed to its interaction with 5-hydroxytryptamine(1D) (5-HT1D) receptors in cer ebral blood vessels and/or on nerve endings of the trigeminovascular s ystem in the dura mater. Using the high sensitivity of polymerase chai n reaction (PCR) amplification, we investigated the expression of the sumatriptan-sensitive 5-HT receptors, namely, the 5-HT1D alpha, 5-HT1D beta, and 5-HT1F subtypes in human trigeminal ganglia (10 experiments ) and cerebral blood vessels (seven experiments) obtained postmortem. Messages for the 5-HT1D alpha and 5-HT1D beta receptors were expressed in all except one of the 10 trigeminal ganglia studied. Expression of the 5-HT1F receptor was detected by gel electrophoresis of the PCR pr oducts in six ganglia and by Southern blot hybridization in two additi onal cases. In human brain vessels, message for the 5-HT1D beta recept or was present in all samples, whereas specific PCR products correspon ding to the 5-HT1D alpha receptor could hardly be detected in only two preparations. PCR products indicative of the 5-HT1F receptor message were detected by gel electrophoresis in three brain vessel preparation s and confirmed in the other four by Southern blot hybridization. Rest riction mapping and sequence analysis of all PCR products identified t he expected human 5-HT receptor DNA sequences. The data confirm that t he 5-HT1D beta receptor is the dominant species in human cerebral bloo d vessels and further show that this receptor and the 5-HT1F are expre ssed in both neural and vascular tissues. In contrast, the data point to a preferential expression of 5-HT1D alpha receptors in neural versu s vascular tissues and strongly reemphasize the need for selective 5-H T1D alpha agonists in the identification of the target tissue(s) for a ntimigraine drugs. Moreover, the data stress the importance to better understand the role of 5-HT1F receptors in cerebrovascular functions a nd dural inflammation and further raise interest regarding their possi ble involvement in migraine therapy.