Participation of 5‐HT₁‐like and 5‐HT_2A receptors in the contraction of human temporal artery by 5‐hydroxytryptamine and related drugs

Abstract

1 We investigated the hypothesis that, as in some other large human arteries, 5-HT-induced contraction of the temporal artery is mediated through two co-existing receptor populations, 5-HT,-like-and 5-HT2A. Temporal arterial segments were obtained from patients undergoing brain surgery and rings prepared set up to contract with 5-HT and related agents. 2 In rings with intact endothelium 5-HT evoked contractions with a -log EC50, M of 7.0. Ketanserin (10-1000 nM) antagonized part of the 5-HT-induced contractions. Ketanserin-resistant components of 5-HT-induced contractions were found with -log EC50, M of 6.9 and f1 of 0.17 (100 nM ketanserin) andlog ECso M of 6.4 and f, of 0.20 (1000 nM ketanserin).3 In rings with endothelial function attenuated by enzymatic treatment, 5-HT caused contractions with a -log EC50, M of 7.2 that were partially blocked by ketanserin. Ketanserin-resistant components of 5-HT-induced contractions were found with -log EC50, M 7.4 and f1 of 0.16 (100 nM ketanserin) and -log EC50, M of 7.5 and fi of 0.14 (1000 nM ketanserin). 4 The ketanserin-resistant component of 5-HT-evoked contraction was blocked by methiothepin (100-1000 nM) consistent with mediation through 5-HT,-like receptors. 5 In rings with intact endothelium the 5-HT1-like-selective agonist, sumatriptan, caused small contractions with a -log EC50, M of 6.5 and intrinsic activity of 0.21 with respect to 5-HT that were resistant to blockade by 1000 nM ketanserin but antagonized by 100 nM methiothepin. 6 In rings with intact endothelium the 5-HT2A receptor partial agonist SK&F 103829 (2,3,4,5-tetrahydro-8[methyl sulphonyl]-1H3-benzazepin-7-ol methensulphonate) contracted rings with a -log EC50, M of 5.0 and an intrinsic activity of 0.49 with respect to 5-HT; the effects were antagonized by ketanserin 1000 nM. 7 We conclude that 80-86% of the maximum 5-HT-evoked contraction of human temporal artery is

5‐HT1B‐receptors and vascular reactivity in human isolated blood vessels: assessment of the potential craniovascular selectivity of sumatriptan

“…For uterine artery and saphenous vein the sumatriptan response was smaller (< 50% relative to 5‐HT) indicating the involvement of both 5‐HT 1B ‐receptors and a larger 5‐HT 2 ‐receptor component [5]. In contrast in temporal artery, sumatriptan was a weak vasoconstrictor consistent with the absence of 5‐HT 1B ‐receptor immunoreactivity [4].…”

“…5‐HT receptors can be classified in 14 distinct subtypes and 5‐HT 1 ‐, 5‐HT 2 ‐ and 5‐HT 7 ‐receptors have been demonstrated to mediate changes in vascular tone [1]. 5‐HT 7 ‐receptor activation causes vasorelaxation [2, 3], whereas 5‐HT 1B/1D ‐receptors and/or 5‐HT 2A ‐receptors, which are negatively linked to adenylate cyclase, mediate vasoconstriction [4–6]. 5‐HT 1F ‐receptors are also negatively coupled to adenylate cyclase [1] and mRNA coding for this receptor subtype is expressed in vascular smooth muscle cells, however, activation of this receptor does not directly influence vascular tone [7, 8].…”

5‐HT1B receptor‐mediated contractions in human temporal artery: evidence from selective antagonists and 5‐HT receptor mRNA expression

“…We have recently proposed that 5‐hydroxytryptamine (5‐HT) contracts human temporal artery through both 5‐HT 1‐like receptors and 5‐HT 2A receptors (Verheggen et al , 1996). Sumatriptan also caused contractions through 5‐HT 1‐like receptors but not 5‐HT 2A receptors.…”

“…The 5‐HT like receptors that mediate contraction could correspond either to the recombinant 5‐HT 1B (ex 5‐HT 1Dβ ) receptor or to the recombinant 5‐HT 1D (ex 5‐HT 1Dcα ) receptor (as reviewed by Hoyer et al , 1994; Hartig et al , 1996); both display a remarkably similar pharmacology (as reviewed by Kaumann et al , 1993). Verheggen et al (1996) suggested that the 5‐HT 1‐like receptors of temporal artery were more likely to be 5‐HT 1B than 5‐HT 1D , due to the failure of ketanserin to cause blockade at 1 μM, a concentration that would be expected to block 5‐HT 1D receptors but not 5‐HT 1B receptors (Kaumann et al , 1994).…”

Serotonin and Blood Pressure Regulation

“…UK, unknown receptor mechanism. Data were collected from the following references: Lemberger et al, 1984;Miller et al, 1984;Feniuk et al, 1985;Nyborg and Mikkelsen, 1985;Cohen, 1986;Leff et al, 1987;Hamel et al, 1989Hamel et al, , 1993Parsons et al, 1989Parsons et al, , 1992Bodelsson et al, 1990;Borton et al, 1990;Chester et al, 1990;Gaw et al, 1990;Mylecharane, 1990;Toda and Okamura, 1990;van Heuven-Nolsen et al, 1990;Asher et al, 1991;Lai et al, 1991;Parsons, 1991;Sumner, 1991;Cohen, 1992a,b, 1993;Dorigo et al, 1992;Eglen et al, 1992;Weiner et al, 1992;Bax et al, 1993;Glusa and Mü ller-Schweinitzer, 1993;Jansen et al, 1993;Cushing et al, 1994Cushing et al, , 1996Yildiz and Tuncer, 1994;Fujiwara and Chiba, 1995;Miranda et al, 1995;Schmuck et al, 1996;Terrón, 1996;Valentin et al, 1996;Verheggen et al, 1996Verheggen et al, , 1998Verheggen et al, , 2004Verheggen et al, , 2006Zwaveling et al, 1996;…”