Evidence for 5‐HT1‐like receptor‐mediated vasoconstriction in human pulmonary artery

1 The 5‐hydroxytryptamine (5‐HT) receptors mediating contraction of human isolated pulmonary artery rings were investigated. Responses to the agonists 5‐carboximidotryptamine (5‐CT, non‐selective 5‐HT1 agonist), sumatriptan (5‐HT1D‐like receptor agonist), 5‐HT and 8‐hydroxy‐2‐(di‐n‐propylamino)‐tetralin (8‐OH‐DPAT, 5‐HT1A receptor agonist) were studied. Responses to 5‐HT and sumatriptan in the presence of the antagonists, methiothepin (non‐selective 5‐HT1+2‐receptor antagonist), ketanserin (5‐HT2A receptor antagonist) and the novel antagonist, GR55562 (5‐HT1D receptor antagonist) were also studied. 2 All agonists contracted human pulmonary artery ring preparations in the following order of potency 5‐CT > 5‐HT = sumatriptan > 8‐OH‐DPAT. Maximum responses to 5‐HT, 5‐CT and sumatriptan were not significantly different. 3 Methiothepin 1 nM and 10 nM, but not 0.1 nM reduced the maximum contractile responses to 5‐HT but did not alter tissue sensitivity to 5‐HT. Methiothepin 0.1 nM, 1 nM and 10 nM had a similar effect on responses to sumatriptan. 4 The 5‐HT2A receptor antagonist ketanserin (10 nM, 100 nM and 1 μm) also reduced the maximum contractile response to both 5‐HT and sumatriptan without affecting tissue sensitivity to these agonists. 5 The novel 5‐HT1D receptor antagonist, GR55562, inhibited responses to 5‐HT and sumatriptan in a true competitive fashion. 6 The results suggest that the human pulmonary artery has a functional population of 5‐HT1D‐like receptors which are involved in the contractile response to 5‐HT.