EVIDENCE FOR 5-HT1-LIKE RECEPTOR-MEDIATED VASOCONSTRICTION IN HUMAN PULMONARY-ARTERY

1 The 5-hydroxytryptamine (5-HT) receptors mediating contraction of hu man isolated pulmonary artery rings were investigated. Responses to th e 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 stud ied. Responses to 5-HT and sumatriptan in the presence of the antagoni sts, methiothepin (non-selective 5-HT1+2-receptor antagonist), ketanse rin (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 po tency 5-CT > 5-HT = sumatriptan > 8-OH-DPAT. Maximum responses to 5-HT , 5-CT and sumatriptan were not significantly different. 3 Methiothepi n 1 nM and 10 nM, but not 0.1 nM reduced the maximum contractile respo nses to 5-HT but did not alter tissue sensitivity to 5-HT. Methiothepi n 0.1 nM, 1 nM and 10 nM had a similar effect on responses to sumatrip tan. 4 The 5-HT2A receptor antagonist ketanserin (10 nM, 100 nM and 1 mu M) also reduced the maximum contractile response to both 5-HT and s umatriptan without affecting tissue sensitivity to these agonists. 5 T he novel 5-HT1D receptor antagonist, GR55562, inhibited responses to 5 -HT and sumatriptan in a true competitive fashion. 6 The results sugge st that the human pulmonary artery has a functional population of 5-HT 1D-like receptors which are involved in the contractile response to 5- HT.