The 5-HT₁ receptors inhibiting the rat vasodepressor sensory CGRPergic outflow: Further involvement of 5-HT_1F, but not 5-HT_1A or 5-HT_1D, subtypes

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• 作者：Abimael Gonzá ; lez-Herná ; ndez^a ; Guadalupe Manrique-Maldonado^a ; Jair Lozano-Cuenca^a ; Enriqueta Mu&#xf1 ; oz-Islas^a ; ¹ ; David Centuri&#xf3 ; n^a ; Antoinette Maassen VanDenBrink^b ; Carlos M. Villal&#xf3 ; n^a ; ^{cvillalon@cinvestav.mx"" rel=""nofollow} ;
• 关键词：Blood pressure ; CGRP (calcitonin gene-related peptide) ; LY344864 ; PNU-142633 ; Sumatriptan
• 刊名：European Journal of Pharmacology
• 出版年：2011
• 出版时间：1 June 2011
• 年：2011
• 卷：659
• 期：2-3
• 页码：233-243
• 全文大小：1030 K

文摘

We have previously shown that 5-HT_1B receptors inhibit prejunctionally the rat vasodepressor CGRPergic sensory outflow. Since 5-HT₁ receptors comprise 5-HT_1A, 5-HT_1B, 5-HT_1D and 5-HT_1F functional subtypes, this study has further investigated the role of 5-HT_1A, 5-HT_1D and 5-HT_1F receptor subtypes in the inhibition of the above vasodepressor sensory outflow. Pithed rats were pretreated with i.v. continuous infusions of hexamethonium and methoxamine, followed by 5-HT₁ receptor agonists. Then electrical spinal stimulation (T₉–T₁₂) or i.v. bolus injections of exogenous α-CGRP produced frequency-dependent or dose-dependent vasodepressor responses. The electrically-induced vasodepressor responses remained unchanged during infusions of the 5-HT_1A receptor agonists 8-OH-DPAT and NN-DP-5-CT. In contrast, these responses were inhibited by the agonists sumatriptan (5-HT_1A/1B/1D/1F), indorenate (5-HT_1A), PNU-142633 (5-HT_1D) or LY344864 (5-HT_1F), which did not affect the vasodepressor responses to exogenous CGRP (implying a prejunctional sensory-inhibition). When analysing the effects of antagonists: (i) 310 μg/kg (but not 100 μg/kg) GR127935 (5-HT_1A/1B/1D/1F) abolished the inhibition to sumatriptan, indorenate, PNU-142633 or LY344864; (ii) 310 μg/kg SB224289 (5-HT_1B) or BRL15572 (5-HT_1D) failed to block the inhibition to sumatriptan or PNU-142633, whereas SB224289 + BRL15572 partly blocked the inhibition to sumatriptan; and (iii) 10 μg/kg WAY100635 (5-HT_1A) failed to block the inhibition to indorenate. These results suggest that 5-HT_1F, but not 5-HT_1A or 5-HT_1D, receptor subtypes inhibit the vasodepressor sensory CGRPergic outflow although, admittedly, no selective 5-HT_1F receptor agonist is available yet. The pharmacological profile of these receptors resembles that shown in rat dorsal root ganglia by molecular biology techniques.