Article date: January 1999
By: Razzaque, Heald, Pickard, Maskell, Beer, Hill, Longmore, in Volume 47, Issue 1, pages 75-82
Aims Sumatriptan is a 5‐HT1B/1D‐receptor agonist which also has affinity for 5‐HT1F‐receptors. The vasoconstrictor effects of sumatriptan are thought to be 5‐HT1B‐receptor mediated and these receptors have been shown to be expressed in human cranial blood vessels. However, in the same tissue mRNA coding for 5‐HT1F‐receptors has also been identified and this study addresses the possibility of whether 5‐HT1F‐receptor activation contributes to vasoconstriction.
Methods The ability of two selective 5‐HT1B/1D‐receptor antagonists (GR125,743 and GR127,935) with no affinity for 5‐HT1F‐receptors, to inhibit sumatriptan evoked contractions in human isolated middle meningeal artery was investigated. Using a series of 5‐HT1B/1D‐receptor agonists (sumatriptan, zolmitriptan, CP122,288, L‐741,519 and L‐741,604), some with high affinity for 5‐HT1F‐receptors and the non‐selective 5‐HT‐receptor agonists 5‐HT and 5‐CT, we compared the vasoconstrictor potency of these drugs in human isolated middle meningeal artery with their affinities at cloned human 5‐HT1B‐, 5‐HT1D‐and 5‐HT1F‐receptors expressed in CHO cell lines.
Results GR125,743 antagonized sumatriptan evoked contractions in a competitive manner (apparent pA2 9.1) and GR127,935 antagonized sumatriptan‐induced responses in a non‐competitive manner (reducing the maximum contraction to 27%). There was a significant correlation between vasoconstrictor potency and 5‐HT1B‐receptor affinity (r=0.93, P=0.002) but not with 5‐HT1D‐ or 5‐HT1F‐receptor affinity (r=0.74, P=0.06; r=0.31, P=0.49, respectively).
Conclusions These experiments show that in human middle meningeal artery vasoconstriction to sumatriptan‐like agents is 5‐HT1B‐receptor mediated with little if any contribution from 5‐HT1F‐receptor activation.
DOI: 10.1046/j.1365-2125.1999.00851.x
View this article