title: Predominant role of the dopamine D3 receptor subtype for mediating the quinpirole-induced inhibition of the vasopressor sympathetic outflow in pithed rats.
abstract: 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.
authors: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, 14330, Mexico DF, Mexico.
authors: Inna
authors: I
authors: Ruiz-Salinas
authors: Abimael
authors: A
authors: González-Hernández
authors: Guadalupe
authors: G
authors: Manrique-Maldonado
authors: Bruno A
authors: BA
authors: Marichal-Cancino
authors: Alain H
authors: AH
authors: Altamirano-Espinoza
authors: Carlos M
authors: CM
authors: Villalón
mesh_terms: D000818:Animals; D018491:Dopamine Agonists / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D008297:Male; D019257:Quinpirole / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D050637:Receptors, Dopamine D3 / Q000819:agonists* / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*
chemical_list: D018491:Dopamine Agonists; D050637:Receptors, Dopamine D3; D014662:Vasoconstrictor Agents; D019257:Quinpirole