Involvement of 5-HT1B and 5-HT1D receptors in sumatriptan mediated vasocontractile response in rabbit common carotid artery

1 In this study we examined the involvement of 5-HT1B and 5-HT1D receptors in the vasocontractile response induced by 5-HT1B/D-receptor agonist sumatriptan in rabbit common carotid artery (CCA). Immunoblotting experiments using specific antisera against 5-HT1B or 5-HT1D receptors revealed the presence of one weak (at 93 kD for 5-HT1B or at 105 kD for 5-HT1D) and one strong band (at 46 kD for 5-HT1B or at 52 kD for 5-HT1D) in CCA. Sumatriptan-mediated vasocontractile response was antagonized by SB216641 with an apparent pKb value of 8.6, which was consistent with its affinity for 5-HT1B receptor. Antagonism by BRL15572 was weak and calculated apparent pKb (6.0) value was consistent with its affinity for 5-HT1B subtype (but not for 5-HT1D subtype). This result indicates insignificant or no involvement of 5-HT1D receptor in the vasocontractile response. The vasocontractile response induced by sumatriptan was highly sensitive to pertussis toxin treatment of CCA. Nicardipine, a calcium channel blocker, also potently antagonized vasocontractile response induced by sumatriptan. 5-HT, but not sumatriptan, stimulated inositol phosphate accumulation in CCA. These results indicate that stimulation of 5-HT1B subtype activate a pertussis toxin (PTX) sensitive G protein (Go/Gi) and mediate vasocontraction, in which L-type voltage dependent calcium channels are involved.