title: The role of dopamine D2, but not D3 or D4, receptor subtypes, in quinpirole-induced inhibition of the cardioaccelerator sympathetic outflow in pithed rats.
abstract: OBJECTIVE
  Quinpirole (a dopamine D2-like receptor agonist) inhibits the cardioaccelerator sympathetic outflow in pithed rats by sympathoinhibitory D2-like receptors. The present study was designed to identify pharmacologically the specific D2-like receptor subtypes (i.e. D2 , D3 and D4) involved in this sympathoinhibition by quinpirole.
  
  
  METHODS
  One hundred fourteen male Wistar rats were pithed, artificially ventilated with room air and prepared for either preganglionic spinal (C7-T1) stimulation of the cardioaccelerator sympathetic outflow (n = 102) or i.v. bolus injections of exogenous noradrenaline (n = 12). This approach resulted in frequency-dependent and dose-dependent tachycardic responses, respectively, as previously reported by our group.
  
  
  RESULTS
  I.v. continuous infusions of quinpirole (0.1-10 μg kg(-1)  min(-1)), but not of saline (0.02 mL min(-1)), dose-dependently inhibited the sympathetically induced tachycardic responses. Moreover, the cardiac sympathoinhibition induced by 3 μg kg(-1)  min(-1) quinpirole (which failed to affect the tachycardic responses to i.v. noradrenaline) was: (i) unchanged after i.v. injections of the antagonists SB-277011-A (D3 ; 100-300 μg kg(-1)) or L-745,870 (D4 ; 30-100 μg kg(-1)); and (ii) markedly blocked and abolished by, respectively, 100 and 300 μg kg(-1) of the D2 preferring receptor subtype antagonist L-741,626. These doses of antagonists, which did not affect per se the sympathetically induced tachycardic responses, were high enough to completely block their respective receptors.
  
  
  CONCLUSIONS
  The cardiac sympathoinhibition induced by 3 μg kg(-1)  min(-1) quinpirole involves the dopamine D2 receptor subtype, with no evidence for the involvement of the D3 or D4 subtypes. This provides new evidence for understanding the modulation of the cardioaccelerator sympathetic outflow.
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, México D.F., México.
authors.forename: A H
authors.initials: AH
authors.lastname: Altamirano-Espinoza
authors.forename: A
authors.initials: A
authors.lastname: González-Hernández
authors.forename: G
authors.initials: G
authors.lastname: Manrique-Maldonado
authors.forename: B A
authors.initials: BA
authors.lastname: Marichal-Cancino
authors.forename: I
authors.initials: I
authors.lastname: Ruiz-Salinas
authors.forename: C M
authors.initials: CM
authors.lastname: Villalón
mesh_terms: D000818:Animals; D003655:Decerebrate State; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage; D019257:Quinpirole / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000187:drug effects / Q000378:metabolism; D050638:Receptors, Dopamine D4 / Q000187:drug effects / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D013566:Sympathomimetics / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; C493595:Drd3 protein, rat; C493601:Drd4 protein, rat; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013566:Sympathomimetics; D050638:Receptors, Dopamine D4; D019257:Quinpirole; D009638:Norepinephrine
keywords: L-741,626; L-745,870; SB-277011-A; cardioaccelerator sympathetic outflow; dopamine D2-like receptors; sympathoinhibition; tachycardic responses
references.citation: Clin Sci (Lond). 2001 Oct;101(4):377-83
references.pmid: 11566075
references.citation: Pharmacol Rev. 1985 Jun;37(2):165-216
references.pmid: 2996038
references.citation: Clin Pharmacol Ther. 1985 Apr;37(4):372-5
references.pmid: 3978997
references.citation: Pharmacol Rev. 2011 Mar;63(1):182-217
references.pmid: 21303898
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 1984 Jun;326(2):91-8
references.pmid: 6089003
references.citation: Clin Exp Hypertens A. 1987;9(5-6):837-51
references.pmid: 3621629
references.citation: Hypertension. 2001 Sep;38(3):303-8
references.pmid: 11566895
references.citation: Neuroreport. 2000 Aug 3;11(11):2467-71
references.pmid: 10943705
references.citation: Pharmacol Rev. 1972 Mar;24(1):1-29
references.pmid: 4554480
references.citation: Br J Pharmacol. 2010 Aug;160(7):1573-6
references.pmid: 20649560
references.citation: J Pharmacol Exp Ther. 1997 Nov;283(2):636-47
references.pmid: 9353380
references.citation: Nephron Physiol. 2003;95(2):p19-27
references.pmid: 14610323
references.citation: Br J Clin Pharmacol. 1985 Jan;19(1):21-7
references.pmid: 2858215
references.citation: J Pharmacol Exp Ther. 2000 Sep;294(3):1154-65
references.pmid: 10945872
references.citation: Trends Pharmacol Sci. 1994 Jul;15(7):264-70
references.pmid: 7940991
references.citation: Fundam Clin Pharmacol. 1992;6(2):67-73
references.pmid: 1351472
references.citation: Br J Pharmacol. 2011 Nov;164 Suppl 1:S1-324
references.pmid: 22040146
references.citation: Hypertension. 1999 Sep;34(3):398-402
references.pmid: 10489384
references.citation: Pharmacol Rev. 2002 Mar;54(1):43-99
references.pmid: 11870260
references.citation: Clin Exp Pharmacol Physiol. 2004 Dec;31(12):837-41
references.pmid: 15659045
references.citation: Life Sci. 1999;64(20):1839-47
references.pmid: 10350358
references.citation: Fundam Clin Pharmacol. 1987;1(3):179-200
references.pmid: 2892767
references.citation: Clin Exp Pharmacol Physiol. 2002 May-Jun;29(5-6):412-8
references.pmid: 12010185
references.citation: Clin Pharmacol Ther. 1984 Dec;36(6):738-44
references.pmid: 6388954
references.citation: Br J Pharmacol. 1996 Dec;119(7):1491-7
references.pmid: 8968560
references.citation: Br J Pharmacol. 1970 Oct;40(2):257-67
references.pmid: 5275866
references.citation: J Recept Signal Transduct Res. 2004 Aug;24(3):165-205
references.pmid: 15521361
references.citation: Br J Pharmacol. 2003 Oct;140(4):725-35
references.pmid: 14504136
references.citation: Curr Opin Neurobiol. 2009 Jun;19(3):245-53
references.pmid: 19559598
references.citation: Br J Pharmacol. 1998 Jul;124(5):1001-11
references.pmid: 9692787
references.citation: Br J Clin Pharmacol. 1986 Jan;21(1):53-61
references.pmid: 2868748
references.citation: Physiol Rev. 1998 Jan;78(1):189-225
references.pmid: 9457173
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2004 Feb;369(2):220-7
references.pmid: 14673512
references.citation: Br J Pharmacol. 2013 Nov;170(5):1102-11
references.pmid: 24032529
references.citation: Br J Clin Pharmacol. 1984 Apr;17(4):373-8
references.pmid: 6721983
references.citation: Arzneimittelforschung. 1986 May;36(5):793-6
references.pmid: 3755340
references.citation: J Appl Physiol. 1964 Mar;19:360-2
references.pmid: 14155315
references.citation: Pharmacol Toxicol. 1990 Apr;66(4):237-43
references.pmid: 2196552
references.citation: Proc Soc Exp Biol Med. 1947 Apr;64(4):453-5
references.pmid: 20239456
references.citation: Eur J Pharmacol. 2009 Jun 10;612(1-3):80-6
references.pmid: 19356724
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2013 May;386(5):393-403
references.pmid: 23420100