Endothelium-dependent relaxation of porcine pulmonary arteries via 5-HT1C-like receptors

Abstract

In PGF2 alpha-precontracted pulmonary arteries with intact endothelium, 5-hydroxytryptamine (5-HT, 1.0-100 nmol/l) caused a concentration-dependent reversible relaxation, at higher concentrations the contractile response prevailed. In endothelium-denuded vessels relaxation was absent. 5-HT-induced relaxation of precontracted pulmonary arteries was probably mediated by release of an endothelium-derived relaxing factor (EDRF). Preincubation of the arteries with methylene blue or NG-nitro-L-arginine (200 mumol/l) attenuated the relaxant effect. The 5-HT-induced relaxation was accompanied by an increase in cGMP. Indomethacin (3 mumol/l) did not influence the 5-HT-induced relaxation indicating that eicosanoids are not involved in the relaxant response to 5-HT. The 5-HT1C and 5-HT2 receptor agonist alpha-methyl-5-HT was as potent as 5-HT in inducing relaxation. The rank order of relaxant potency of the agonists investigated was alpha-methyl-5-HT > 5-HT > 5-methoxytryptamine > tryptamine > omega-methyl-5-HT > 5-carboxamidotryptamine > 2-methyl-5-HT > 5,6-dihydroxytryptamine > m-chlorophenylpiperazine > sumatriptan > 8-OH-DPAT. Phentolamine, pindolol and ICS 205-930 did not interfere with the relaxant effect. The 5-HT2 receptor antagonist ketanserin (1 mumol/l) inhibited the contractile response but did not alter vasodilatation. Apart from the blockade of the contractile effects, mesulergine, cyproheptadine and mianserin (0.1-3.0 mumol/l, each) induced a parallel shift to the right of the concentration-response curve for the relaxation induced by alpha-methyl-5-HT or 5-HT. Spiperone (0.3 mumol/l) exerted weak inhibitory effects on relaxation and contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

5‐Hydroxytryptamine receptors mediating vasoconstriction and vasodilation in perinatal and adult rabbit small pulmonary arteries

“…This explanation is, however, unlikely in our preparation as we have shown that fetal and 0 ± 24 h rabbit PRAs relax to acetylcholine . 5-HT receptors are known to mediate vasodilation in blood vessels either directly via 5-HT receptors located on the vascular smooth muscle (Cocks & Arnold, 1992;Leung et al, 1996) or indirectly via endothelial released NO (Bodelson et al, 1993;Glusa & Richter, 1993;Glusa & Roos, 1996). We show that, in 4-and 7-day-old rabbit small pulmonary arteries, 5-CT-evoked vasodilation is inhibited by the NO synthase inhibitor L-NAME.…”

“…5-HT has previously been shown to elicit endotheliumdependent relaxation in porcine pulmonary arteries (Glusa & Richter, 1993) as well as other, systemic preparations (Bodelson et al, 1993). Using 5-CT, we established that there is 5-HT-receptor-induced vasodilation present in the vessels from the 4-and 7-day-old rabbits.…”

“…5-HT causes vasoconstriction in isolated bovine intrapulmonary arteries via a 5-HT 1D/1B receptor (MacLean et al, 1994) but induces endothelium-dependent relaxation in isolated porcine pulmonary arteries via the`5-HT 1C ' receptor (Glusa & Richter, 1993). The 5-HT 1C receptor has subsequently been renamed the 5-HT 2C receptor (Hoyer et al, 1994).…”

PDZ-dependent Activation of Nitric-oxide Synthases by the Serotonin 2B Receptor

“…Mastomys carcinoid tumor primary cultures, clonal neural-like 1C11* /5HT serotonergic cells and 5-HT 2B receptor transfected LM6 fibroblasts, the 5-HT 2 receptor agonist DOI (or 5-HT, data not shown) always triggers intracellular cGMP accumulation resulting from both cNOS and iNOS activation. Such a link between 5-HT and NO could already be suspected in view of the simultaneous involvement of these two agents in smooth muscle contractility (6,30), vascular contraction (7,31), and related migraine pathogenesis (32). Because 5-HT 2B receptors are present in stomach, intestine, pulmonary smooth muscles, kidney, as well as in myocardium, vascular endothelium, and meningeal tissues (3,33,34), they are obvious candidates to trigger the NO response associated to 5-HT.…”

Participation of 5‐HT1‐like and 5‐HT2A receptors in the contraction of human temporal artery by 5‐hydroxytryptamine and related drugs

“…The blocking potency of ketanserin (effective at 100 nM and higher concentrations) against the relaxant components of 5-HT-induced phasic contractions in the temporal artery is so far consistent with the interaction with 5-HT2c receptors and/or 5-HT2B receptors. It has previously been suggested that endothelial 5-HT2c receptors mediate 5-HT-induced relaxation in porcine pulmonary artery (Glusa & Richter, 1993) and rat jugular vein (Bodelsson et al, 1993), but ketanserin (1 gM) failed to cause antagonism, which is inconsistent with its submicromolar affinity for 5-HT2c receptors and leaves open the possibility of mediation through 5-HT2B receptors. Ellis et al (1995) have indeed recently suggested that endothelium-dependent relaxation of rat jugular vein by 5-HT is mediated through 5-HT2B…”