E. Martínez-García, B. García-Iglesias, J. A. Terrón
{"title":"Effect of central serotonin depletion on 5-HT receptor-mediated vasomotor responses in the middle meningeal artery of anaesthetized rats","authors":"E. Martínez-García, B. García-Iglesias, J. A. Terrón","doi":"10.1111/j.1474-8673.2009.00430.x","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p> <b>1</b> It has been hypothesized that craniovascular 5-HT receptors mediating dilatation of cranial vessels undergo sensitization on decreased serotonergic transmission in migraine. This study analysed the effect of chemical lesion of the 5-HT system in the brain with 5,7-dihydroxytryptamine (5,7-DHT) on 5-HT receptor-mediated dilator responses to 5-carboxamidotryptamine (5-CT) in the middle meningeal artery of anaesthetized rats. 5-CT has recently been shown to elicit dilator responses in this cranial vessel via 5-HT<sub>7</sub> receptors and, to a much lesser extent, 5-HT<sub>1B/1D</sub> receptors.</p>\n <p> <b>2</b> Pretreatment with 5,7-DHT produced a drastic and selective decrease of 5-HT levels in the brain (78 ± 6% and 94 ± 2% in dorsal raphe and hypothalamic paraventricular nuclei, respectively) compared with controls (1% ascorbic acid).</p>\n <p> <b>3</b> Topical application of 5-CT (1–1000 μ<span>m</span>) to exposed dura mater encephali produced concentration-dependent decreases in diastolic blood pressure and dilator responses in the middle meningeal artery that were similar in vehicle- and 5,7-DHT-pretreaed animals.</p>\n <p> <b>4</b> Hypotensive and meningeal dilator responses to 5-CT were unaltered by the 5-HT<sub>1B/1D</sub> receptor antagonist, GR-127935 (1 mg kg<sup>−1</sup>, i.v.), but were strongly inhibited by the 5-HT<sub>7</sub> receptor antagonist, SB-269970 (1 mg kg<sup>−1</sup>, i.v.), with similar efficacy, in both groups of animals. Treatment with GR-127935 + SB-269970 (1 mg kg<sup>−1</sup>, i.v. each), produced a stronger inhibitory effect than individual treatments on hypotensive but not on meningeal responses to 5-CT. Meningeal 5-HT<sub>7</sub> receptor-mediated responses (i.e. in GR-127935-pretreated animals) were unchanged by 5,7-DHT pretreatment.</p>\n <p> <b>5</b> Results suggest that the sensitivity of craniovascular 5-HT<sub>7</sub> receptors mediating dilatation is unaffected by a decrease of 5-HT levels in the brain. A neuronal involvement of 5-HT in migraine seems more likely, therefore.</p>\n </div>","PeriodicalId":100151,"journal":{"name":"Autonomic and Autacoid Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2009-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1474-8673.2009.00430.x","citationCount":"10","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Autonomic and Autacoid Pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/j.1474-8673.2009.00430.x","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 10
Abstract
1 It has been hypothesized that craniovascular 5-HT receptors mediating dilatation of cranial vessels undergo sensitization on decreased serotonergic transmission in migraine. This study analysed the effect of chemical lesion of the 5-HT system in the brain with 5,7-dihydroxytryptamine (5,7-DHT) on 5-HT receptor-mediated dilator responses to 5-carboxamidotryptamine (5-CT) in the middle meningeal artery of anaesthetized rats. 5-CT has recently been shown to elicit dilator responses in this cranial vessel via 5-HT7 receptors and, to a much lesser extent, 5-HT1B/1D receptors.
2 Pretreatment with 5,7-DHT produced a drastic and selective decrease of 5-HT levels in the brain (78 ± 6% and 94 ± 2% in dorsal raphe and hypothalamic paraventricular nuclei, respectively) compared with controls (1% ascorbic acid).
3 Topical application of 5-CT (1–1000 μm) to exposed dura mater encephali produced concentration-dependent decreases in diastolic blood pressure and dilator responses in the middle meningeal artery that were similar in vehicle- and 5,7-DHT-pretreaed animals.
4 Hypotensive and meningeal dilator responses to 5-CT were unaltered by the 5-HT1B/1D receptor antagonist, GR-127935 (1 mg kg−1, i.v.), but were strongly inhibited by the 5-HT7 receptor antagonist, SB-269970 (1 mg kg−1, i.v.), with similar efficacy, in both groups of animals. Treatment with GR-127935 + SB-269970 (1 mg kg−1, i.v. each), produced a stronger inhibitory effect than individual treatments on hypotensive but not on meningeal responses to 5-CT. Meningeal 5-HT7 receptor-mediated responses (i.e. in GR-127935-pretreated animals) were unchanged by 5,7-DHT pretreatment.
5 Results suggest that the sensitivity of craniovascular 5-HT7 receptors mediating dilatation is unaffected by a decrease of 5-HT levels in the brain. A neuronal involvement of 5-HT in migraine seems more likely, therefore.