Predominant role of the dopamine D3 receptor subtype for mediating the quinpirole-induced inhibition of the vasopressor sympathetic outflow in pithed rats

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• 作者：Inna Ruiz-Salinas (1) r> Abimael González-Hernández (1) r> Guadalupe Manrique-Maldonado (1) r> Bruno A. Marichal-Cancino (1) r> Alain H. Altamirano-Espinoza (1) r> Carlos M. Villalón (1) r>
• 关键词：L ; 741 ; 626 ; L ; 745 ; 870 ; Nafadotride ; SB ; 277011 ; A ; Quinpirole ; Vasopressor sympathetic outflow
• 刊名：Naunyn-Schmiedeberg's Archives of Pharmacology
• 出版年：2013
• 出版时间：May 2013
• 年：2013
• 卷：386
• 期：5
• 页码：393-403
• 全文大小：570KB
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• 作者单位：Inna Ruiz-Salinas (1) r> Abimael González-Hernández (1) r> Guadalupe Manrique-Maldonado (1) r> Bruno A. Marichal-Cancino (1) r> Alain H. Altamirano-Espinoza (1) r> Carlos M. Villalón (1) r>r>1. Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, 14330, Mexico DF, Mexico r>
• ISSN：1432-1912

文摘

We have recently reported that quinpirole (a D2-like receptor agonist) inhibits the vasopressor sympathetic outflow in pithed rats via sympatho-inhibitory D2-like receptors. Since D2-like receptors consist of D2, D3 and D4 receptor subtypes, this study investigated whether these subtypes are involved in the above quinpirole-induced sympatho-inhibition by using antagonists of these receptor subtypes. One hundred fifty-six male Wistar rats were pithed and prepared for preganglionic spinal (T7–T9) stimulation of the vasopressor sympathetic outflow. This approach resulted in frequency-dependent vasopressor responses which were analysed before and during i.v. continuous infusions of either saline (0.02?ml/min) or quinpirole (1?μg/kg.min) in animals receiving i.v. bolus injections of vehicle [saline or dimethyl sulfoxide (DMSO)] or the antagonists L-741,626 (D2), nafadotride or SB-277011-A (both D3) as well as L-745,870 (D4). Quinpirole inhibited the sympathetically-induced vasopressor responses. This sympatho-inhibition was (a) unaltered after 1?ml/kg saline, DMSO or 100 and 300?μg/kg L-741,626; (b) markedly blocked and abolished by, respectively, 30 and 100?μg/kg nafadotride or 100 and 300?μg/kg SB-277011-A and (c) slightly blocked after 30 and 100?μg/kg L-745,870, but 300?μg/kg L-745,870 produced no blockade whatsoever. Except for 300?μg/kg L-741,626 or 300?μg/kg L-745,870, the doses of the above compounds failed to modify per se the sympathetic vasopressor responses. The inhibition of the vasopressor sympathetic outflow induced by 1?μg/kg.min quinpirole in pithed rats is predominantly mediated by dopamine D3 and, to a lesser extent, by D4 receptor subtypes, with no evidence for the involvement of the D2 subtype.