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Evidence for 5‐HT 1 ‐like receptor‐mediated vasoconstriction in human pulmonary artery
Author(s) -
MacLean Margaret R.,
Clayton Robin A.,
Templeton Alison G.B.,
Morecroft Ian
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15982.x
Subject(s) - ketanserin , sumatriptan , agonist , receptor antagonist , 5 ht receptor , medicine , competitive antagonist , pharmacology , endocrinology , antagonist , serotonin , receptor , chemistry
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‐HT 1 agonist), sumatriptan (5‐HT 1D ‐like receptor agonist), 5‐HT and 8‐hydroxy‐2‐(di‐n‐propylamino)‐tetralin (8‐OH‐DPAT, 5‐HT 1A receptor agonist) were studied. Responses to 5‐HT and sumatriptan in the presence of the antagonists, methiothepin (non‐selective 5‐HT 1+2 ‐receptor antagonist), ketanserin (5‐HT 2A receptor antagonist) and the novel antagonist, GR55562 (5‐HT 1D 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‐HT 2A receptor antagonist ketanserin (10 nM, 100 nM and 1 μ m ) also reduced the maximum contractile response to both 5‐HT and sumatriptan without affecting tissue sensitivity to these agonists. 5 The novel 5‐HT 1D 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‐HT 1D ‐like receptors which are involved in the contractile response to 5‐HT.