5-Hydroxytryptamine (5-HT) contracts the guinea-pig isolated iliac artery via 5-HT1-like and 5-HT2 receptors

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Abstract
Summary The characterization of 5-hydroxytryptamine (5-HT) receptors mediating contractions of the guinea-pig isolated iliac artery was studied when the basal tone was slightly increased by prostaglandin F2α (PGF2α). In the presence of ketanserin (1 μmol/l), 5-HT and several 5-HT receptor agonists induced contractile responses with the rank order of agonist potency: 5-HT = 5-carboxamidotryptamine (5-CT) = lysergol > ergometrine = methylergometrine > RU 24969 ≈ 5-methoxytryptamine (5-MeOT) > methysergide > sumatriptan > tryptamine. Concentration-effect curves to the ergot alkaloids, lysergol, ergometrine, methylergometrine and methysergide, were biphasic. In the presence of ketanserin (1 μmol/l), contractile responses to 5-HT, 5-CT, RU 24969, 5-MeOT, sumatriptan and tryptamine were antagonized by methiothepin (30 nmol/l) and flesinoxan (3 μmol/l) with approximate pKB values of 8.5–9.0 and 6.0–6.3, respectively. The first phase of contraction produced by the ergot alkaloids, lysergol, ergometrine, methylergometrine and methysergide, were blocked by methiothepin (30 nmol/l) and flesinoxan (3 μmol/l), respectively, with approximate pKB values about 8.4–8.7 and 6.2–6.4, respectively. The mechanism underlying the second phase of contraction remains to be established. Maximum responses of the concentration-effect curves to 5-HT (1 nmol/l-1 μmol/l) were concentration-dependently depressed by ketanserin (1 nmol/l-1 μmol) and spiperone (30 nmol/l-0.3 μmol/l) and reached approximately 60% of the 5-HT maximum response in the presence of ketanserin (1 μmol/l) and spiperone (0.1 μmol/l), respectively. Agonist potency of 5-HT was not affected by the antagonists. 5-HT (1 nmol/l-1 mmol) produced biphasic concentration-effect curves (first phase: 1 nmol/l-1 gmol/l; second phase: 1 μmol/l-1 mmol/l) in the presence of ketanserin (100 and 300 nmol/l), spiperone (100 and 300 nmol/l), (R)-α-methylketanserin (3 μmol/l) and (S)-α-methylketanserin (10 nmol/l). Contractions mediating the first phase of the effects of 5-HT accounted for approximately 60% of the 5-HT maximum response and were resistant to blockade by the antagonists. pKB values at the receptor mediating the second phase of the effects of 5-HT were 9.2–9.3 for ketanserin, 9.2–9.6 for spiperone, 10.5 for (S)-α-methylketanserin and 7.2 for (R)-α-methylketanserin. It is concluded that 5-HT contracts the guinea-pig isolated iliac artery via a mixture of 5-HT1-like receptors and 5-HT2 receptors. At low concentrations contractions are mediated via 5-HT1-like receptors which accounted for approximately 60% of the 5-HT maximum response. At higher concentrations 5-HT-induced contractions are mediated via 5-HT2 receptors.