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Participation of 5-HT1-like and 5-HT2A receptors in the contraction of human temporal artery by 5-hydroxytryptamine and related drugs
- Source :
- British journal of pharmacology. 117(2)
- Publication Year :
- 1996
-
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-HT1-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. Fractions of maximal 5-HT responses mediated through 5-HT1-like and 5-HT2A receptors, f1 and f2 = 1-f1, were estimated by use of the 5-HT2A-selective antagonist ketanserin. 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) and -log EC50, M of 6.4 and f1 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 f1 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-HT1-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 mediated through 5-HT2A receptors, the remainder through 5-HT1-like-receptors, regardless of whether or not endothelium is functional. The 5-HT1-like-receptors are more likely to be 5-HT1D beta receptors than 5-HT1D alpha receptors and sumatriptan is a full agonist for these receptors. As found in arteries of other species, SK&F 103829 is a partial agonist for 5-HT2A receptors of human temporal artery.
- Subjects :
- Agonist
Adult
Male
medicine.medical_specialty
Serotonin
Ketanserin
Intrinsic activity
medicine.drug_class
In Vitro Techniques
Partial agonist
Muscle, Smooth, Vascular
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Humans
heterocyclic compounds
Collagenases
Receptor
030304 developmental biology
Aged
Pharmacology
0303 health sciences
Chemistry
Sumatriptan
musculoskeletal, neural, and ocular physiology
Headache
Benzazepines
Middle Aged
musculoskeletal system
Serotonin Receptor Agonists
Temporal Arteries
Endocrinology
Receptors, Serotonin
cardiovascular system
5-HT1 receptor
Female
Endothelium, Vascular
Serotonin Antagonists
medicine.symptom
030217 neurology & neurosurgery
Muscle contraction
medicine.drug
Muscle Contraction
Research Article
Subjects
Details
- ISSN :
- 00071188
- Volume :
- 117
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- British journal of pharmacology
- Accession number :
- edsair.doi.dedup.....302bfcabe6071bdb89b3f1f27ecbcd1b