Evidence that 5-HT2 receptors predominantly mediate the contraction of the rat basilar artery to 5-hydroxytryptamine

doi:10.1016/0014-2999(92)90767-X

European Journal of Pharmacology

Volume 221, Issue 1, 6 October 1992, Pages 17-25

https://doi.org/10.1016/0014-2999(92)90767-X Get rights and content

Abstract

We characterised the 5-hydroxytryptamine (5-HT) receptor subtype which mediates the contraction of the rat isolated basilar artery, mounted in a myograph, by using agonists and antagonists for 5-HT₁-like, 5-HT₂, 5-HT₃ AND 5-HT₄, receptors. The rank order of potency for a range of selective agonists was: 5-HT > α-mcthyl-5-HT > 5-carboxamidotryptamine > 2-methyl-5-HT > sumatriptan. The maximum contractions for these agonists (E_max) was less than for 5-HT while 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was devoid of contractile activity. Ketanserin antagonised the contractile effect of 5-HT in the rat basilar artery with a provisional pA₂ estimate of 9.3 ± 0.2. A similar antagonism was observed against α-methyl-5-HT. Ergometrine (0.01–1 μM) was devoid of any agonist activity but antagonised the contractile effect of 5-HT on the rat basilar artery with a provisional pK_B of 8.7 (7.8–9.8, 95% confidence limits). The 5-HT₃ and 5-HT₄ receptor antagonist ICS 20593(1 (10 μM) did not alter the response to 5-HT. The high potency and efficacy of α-methyl-5-HT, poor effect of sumatriptan and antagonism of 5-HT by ergometrinc and ketanscrin, support the conclusion that the 5-HT₂, receptors are primarily responsible for the 5-HT-induccd contraction of rat basilar artery.

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Vasoconstrictor 5-HT receptors in the smooth muscle of the rat middle cerebral artery
2012, European Journal of Pharmacology
Citation Excerpt :
Sumatriptan was a more potent vasoconstrictor in human middle meningeal (pEC50=7.0), porcine middle cerebral artery (pEC50=6.55±0.1) and bovine isolated middle cerebral artery (pD2=6.0±0.2) than the potency of the drug in the rat middle cerebral artery (Razzaque et al., 2002; Nagai et al., 2007; Roon et al., 1999). Our results are in agreement with those of Hansen-Schwartz et al. (2003b), who obtained contractile responses to sumatriptan at high concentrations in the rat middle cerebral artery using the same method also applied by us, and other authors also described that sumatriptan is a low potency vasoconstrictor in rat cerebral arteries (Limmroth et al., 1999; Deckert and Angus, 1992). These results fit with weak binding of sumatriptan (Ki=0.5 μM) to the rat 5-HT1B receptor (Adham et al., 1992).
Serotonin (5-HT) can constrict cerebral arteries via activation of 5-HT_1B and 5-HT_2A receptors. Our goal was to reveal the importance and relative contribution of the two 5-HT receptor subtypes to the serotonin-induced vasoconstriction in the rat middle cerebral artery. The vasoconstrictor effects of 5-carboxamidotryptamine, sumatriptan and 5-HT were measured without and with pre-treatment with SB 216641 (5-HT_1B antagonist), or ritanserin, (5-HT_2A antagonist), in endothelium-denuded arteries, in vitro. All agonists caused vasoconstrictions. The order of potency (EC₅₀) of the compounds was: 5-carboxamidotryptamine (14±3 nM)>5-HT (270±30 nM)>sumatriptan (5.8±1.9 μM). The concentration–response curve of 5-carboxamidotryptamine resembled the sum of two sigmoid curves (EC₅₀ 14±3 nM and 15±7 μM), and SB 216641 and ritanserin antagonized its low and high concentration components, respectively. Vasoconstrictions evoked by 5-HT at low and high concentrations were also fully antagonized by SB 216641 and ritanserin, respectively. Sumatriptan constricted the middle cerebral artery exclusively via 5-HT_1B receptors. The efficacy of 5-carboxamidotryptamine and sumatriptan was low in comparison to the maximum contractile force elicited by 120 mmol/l KCl, reaching only 18–23% for 5-HT_1B and 14% for 5-HT_2A receptor activation. In conclusion, 5-HT produced small vasoconstrictions in the rat middle cerebral artery that were mediated by 5-HT_1B receptors with high potency and by 5-HT_2A receptors with low potency. Thus, 5-HT may have a minor physiological role in blood flow regulation via 5-HT_1B receptor activation while 5-HT_2A receptors seem to have a pathophysiological role in this vessel.
Characterization of 5-hydroxytryptamine-induced contraction and acetylcholine-induced relaxation in isolated chicken basilar artery
2012, Poultry Science
Citation Excerpt :
Two 5-HT receptor subtypes in basilar arteries have been recognized, and the nature of these subtypes has been reported to differ in various animal species. The 5-HT-induced contraction of the basilar artery is mediated via activation of 5-HT1 receptors in snakes (Yoshinaga et al., 2007), guinea pigs (Chang and Owman, 1989), rabbits (Seager et al., 1992), and humans (Parsons et al., 1989); 5-HT2 receptors in rats (Chang and Owman, 1989; Deckert and Angus, 1992) and monkeys (Cercopithecus aethiops; Chang et al., 1987); and both 5-HT1 and 5-HT2 receptors in dogs (Connor et al., 1989), horses (Miyamoto et. al., 1996), sheep (Gaw et al., 1990), pigs (Miyamoto et. al., 1994), and monkeys (Macaca fascicularis; Connor et al., 1989). In porcine pulmonary arteries, 5-HT induced relaxation (Cocks and Angus, 1983).
The aim of the present study was to clarify the responsiveness of the chicken basilar artery to 5-hydroxytryptamine (5-HT) and acetylcholine (ACh) and to characterize the related receptor subtypes in vitro. Basilar arteries were obtained from freshly slaughtered broiler chickens. The 5-HT induced concentration-dependent contraction of the arteries. The concentration-response curves for 5-HT were shifted 30-fold to the right by methiothepin (a 5-HT₁ and 5-HT₂ receptor antagonist) and 3-fold to the right by ketanserin (a 5-HT₂ receptor antagonist). In the presence of ketanserin, the concentration-response curve for 5-HT was shifted 10-fold to the right by methiothepin. The pA₂ value for methiothepin was 8.26. The ACh induced concentration-dependent relaxation under conditions of precontraction by 5-HT. The concentration-response curve for ACh was shifted to the right by atropine [a nonselective muscarinic (M) receptor antagonist] and hexahydro-sila-difenidol hydrochloride, a p-fluoroanalog (pFHHSiD, an M₃ receptor antagonist), but not by pirenzepine (an M₁ receptor antagonist) or methoctramine (an M₂ receptor antagonist). The pA₂ value for pFHHSiD was 7.55. Nω-Nitro-l-arginine (a nitric oxide synthase inhibitor) inhibited ACh-induced relaxation by approximately 50%. These results suggest that 5-HT induces contraction via activation of 5-HT₁ and 5-HT₂ receptors and that ACh induces relaxation via activation of the M₃ receptor. The 5-HT₁ receptor might play a dominant role in 5-HT-induced contraction. One of the factors involved in ACh-induced relaxation is probably nitric oxide released from endothelial cells.
Mediation by 5-HT<inf>2</inf> receptors of 5-hydroxytryptamine-induced contractions of human placental vein
1998, General Pharmacology
- 1.
  In isolated human placental chorionic vein segments, 5-hydroxytryptamine (5-HT; 10⁻⁸ to 5×10⁻⁵ M) elicited concentration-dependent contractions with EC₅₀=5.5 (5.2–5.7)×10⁻⁸ M) and E_max=93.1±7.3% of 75 mM KCl-induced contraction.
- 2.
  The agonist of 5-HT₂ receptors, α-methyl-5-hydroxytryptamine, and the selective agonist of 5-HT₁ receptors, N,N-dipropyl-5-carboxamidotryptamine and 5-carboxamidotryptamine, induced pronounced concentration-related contractions, which reached 71.1±6.0%, 53.0±5.0% and 75.0±7.8% at the highest dose tested, respectively. The agonist of 5-HT₃ receptor, 2-methyl-5-hydroxytryptamine, reached a maximum averaging 36.7±5.1% of the maximal response to KCl.
- 3.
  The 5-HT₁ and 5-HT₃ receptor antagonists, methiothepin and metoclopramide (10⁻⁷ to 10⁻⁶ M) did not alter the response to 5-HT. However, ketanserin (10⁻⁷ to 10⁻⁶ M), a 5-HT₂ receptor antagonist, induced significant inhibition of the concentration–response curve to 5-HT.
- 4.
  Contractile responses to 5-carboxamidotryptamine and 2-methyl-5-hydroxytryptamine were not affected by methiothepin and metoclopramide, respectively, whereas ketanserin significantly attenuated the contractile response to these agonists.
- 5.
  In conclusion, our study shows that 5-HT₂ receptors mediate contraction of the human placental vein with no obvious role for 5-HT₁-like, or 5-HT₃ receptors.
Innervation of cerebral arteries by nerves containing 5-hydroxytryptamine and noradrenaline
1995, Pharmacology and Therapeutics
Noradrenaline (NA)-containing nerves, mainly originating in the sympathetic superior cervical ganglia, supply large and small cerebral arteries. In large cerebral arteries, nerves containing serotonin (5-hydroxytryptamine, 5-HT) may represent neuronal uptake of circulating 5-HT by sympathetic nerves. 5-HT-containing nerves supplying small pial vessels probably have a central origin in the dorsal raphe nucleus. In most species, NA is a weak vasoconstrictor (α₁- or α₂-adrenoceptors), while 5-HT is a potent vasoconstrictor (5-HT₂ or 5-HT₁-like receptors) of large cerebral arteries. In contrast, both NA and 5-HT tend to cause vasodilatation in small pial vessels and arterioles. Adrenergic and serotonergic transmission can be modulated by pH, a range of putative neurotransmitters and neuromodulators, and by the endothelium. Sumatriptan, a 5-HT₁-like receptor agonist, has been shown to be effective in the treatment of migraine. Changes in NA- or 5-HT-containing nerves and/or in the responses of cerebral vessels to NA and 5-HT have been observed in a variety of vascular disorders, including cerebral vasospasm following subarachnoid haemorrhage, hypertension, and atherosclerosis.
Endothelial thromboxane production plays a role in the contraction caused by 5-hydroxytryptamine in rat basilar arteries
1993, European Journal of Pharmacology
The goal of the present study was to characterize the role of the endothelium in the 5-hydroxytryptamine (5-HT)-induced contraction of the rat basilar artery. Rat basilar artery segments were mounted in myographs to study their isometric tension development. 5-HT caused dose-dependent contractions that were minimally affected by endothelium removal. The dose-response curve obtained with the 5-HT₁ receptor agonist, 5-carboxamidotryptamine (5-CT), was biphasic in arteries with endothelium; removal of the endothelium eliminated the first phase of the contraction. The 5-HT₂ receptor antagonist, ketanserin (30 nM), shifted the dose-response curve to 5-HT to the right; in arteries with endothelium, the curve became biphasic. Ketanserin inhibited the second phase of the dose-response curve to 5-CT. The mixed 5-HT₁/5-HT₂ receptor antagonist, metergoline (30 nM), shifted the dose-response curve to 5-HT non-competitively to the right and depressed both phases of the dose-response curve to 5-CT. In basilar arteries with endothelium and treated with ketanserin, the thromboxane A₂ receptor antagonist, ICI 192605 (1 μM), significantly decreased the responsiveness to 5-HT and the dose-response curve for 5-HT became monophasic. ICI 192605 and the thromboxane A₂ synthase inhibitor, ridogrel (10 μM), both suppressed the first phase of the dose-response curve to 5-CT. These data indicate that both endothelial 5-HT₁ and smooth muscle 5-HT₂ receptors participate in the contractions caused by 5-HT in the rat basilar artery. Activation of the endothelial 5-HT₁ receptors causes the release of a substance that subsequently activates thromboxane A₂ receptors on the smooth muscle cells; this substance most likely is thromboxane A₂ itself.
5-HT<inf>2B</inf> Receptor, the Heart and Blood Vessels
2021, Receptors

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¹: Present address: Laboratories Fournier, 50 Rue de Dijon, B.P. 90. 21121 Daix, France.

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Evidence that 5-HT2 receptors predominantly mediate the contraction of the rat basilar artery to 5-hydroxytryptamine

Abstract

Lancet

Neuropharmacology

Trends Pharmacol. Sci.

Lancet

Lancet

Brain Res.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Brain Res.

Some quantitative uses of drug antagonists

Br. J. Pharmacol.

Differential vasomolor action of noradrenaline. serolonin and histamine in isolated basilar artery from rat and guinea-pig

Acta Physiol. Scand.

Cerehrovascular serolonergic receptors mediating vasoconstriction: further evidence for the existence of 5-HT2 receptors in rat and 5-HT1-like receptors in guinea-pig basilar arteries

Acta Physiol. Scand.

Relationship between receptors mediating serotonin (5-HT) contractions in the canine basilar artery to 5-HT1, 5-HT2 and the rat stomach fundus 5-HT receptors

J. Pharmacol. Exp. Ther.

Influence of the endothelium on contractile effects of 5-hydroxytryptamine and selective 5-HT agonists in canine hasilar artery

Br. J. Pharmacol.

Characterization of 5-HT receplors mediating contraction of canine and primate basilar artery by use of GR 43175, a selective 5-HT1-like receptor agonist

Br. J. Pharmacol.

Central serotonergic nerves project to the pial vessels of the brain

Nature

Spinal noradrenergic pathways presser responses to central angiotensin II

Am. J. Physiol.

Identity of inhibitory presynaptic 5-hydroxytryptamine (5-HT) autoreceptors in the rat brain cortex with 5-HT1B binding sites

Naunyn-Schmiedeb. Arch. Pharmacol.

Evidence that 5-HT₂ receptors predominantly mediate the contraction of the rat basilar artery to 5-hydroxytryptamine

Cerehrovascular serolonergic receptors mediating vasoconstriction: further evidence for the existence of 5-HT₂ receptors in rat and 5-HT₁-like receptors in guinea-pig basilar arteries

Relationship between receptors mediating serotonin (5-HT) contractions in the canine basilar artery to 5-HT₁, 5-HT₂ and the rat stomach fundus 5-HT receptors

Characterization of 5-HT receplors mediating contraction of canine and primate basilar artery by use of GR 43175, a selective 5-HT₁-like receptor agonist

Identity of inhibitory presynaptic 5-hydroxytryptamine (5-HT) autoreceptors in the rat brain cortex with 5-HT_1B binding sites