title: Purinergic and glutamatergic interactions in the hypothalamic paraventricular nucleus modulate sympathetic outflow.
abstract: P2X receptors are expressed on ventrolateral medulla projecting paraventricular nucleus (PVN) neurons. Here, we investigate the role of adenosine 5'-triphosphate (ATP) in modulating sympathetic nerve activity (SNA) at the level of the PVN. We used an in situ arterially perfused rat preparation to determine the effect of P2 receptor activation and the putative interaction between purinergic and glutamatergic neurotransmitter systems within the PVN on lumbar SNA (LSNA). Unilateral microinjection of ATP into the PVN induced a dose-related increase in the LSNA (1 nmol: 38 ± 6 %, 2.5 nmol: 72 ± 7 %, 5 nmol: 96 ±13 %). This increase was significantly attenuated by blockade of P2 receptors (pyridoxalphosphate-6-azophenyl-20,40-disulphonic acid, PPADS) and glutamate receptors (kynurenic acid, KYN) or a combination of both. The increase in LSNA elicited by L-glutamate microinjection into the PVN was not affected by a previous injection of PPADS. Selective blockade of non-N-methyl-D-aspartate receptors (6-cyano-7-nitroquinoxaline-2,3-dione disodium salt, CNQX), but not N-methyl-D-aspartate receptors (NMDA) receptors (DL-2-amino-5-phosphonopentanoic acid, AP5), attenuated the ATP-induced sympathoexcitatory effects at the PVN level. Taken together, our data show that purinergic neurotransmission within the PVN is involved in the control of SNA via P2 receptor activation. Moreover, we show an interaction between P2 receptors and non-NMDA glutamate receptors in the PVN suggesting that these functional interactions might be important in the regulation of sympathetic outflow.
authors: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors: H C
authors: HC
authors: Ferreira-Neto
authors: S T
authors: ST
authors: Yao
authors: V R
authors: VR
authors: Antunes
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D004594:Electrophysiology; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D058469:Receptors, Purinergic P2X / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
chemical_list: D058469:Receptors, Purinergic P2X; D000255:Adenosine Triphosphate
references: Br J Pharmacol. 1997 Oct;122(3):423-30
references: 9351497
references: Annu Rev Neurosci. 1983;6:269-324
references: 6132586
references: Hypertension. 2003 Oct;42(4):725-31
references: 12900439
references: J Appl Physiol (1985). 1992 Apr;72(4):1247-54
references: 1592711
references: J Comp Neurol. 1980 Dec 1;194(3):555-70
references: 7451682
references: J Neurochem. 2010 Apr;113(2):530-42
references: 20096091
references: J Gen Physiol. 2007 Mar;129(3):257-65
references: 17325196
references: Neuroscience. 1999;94(3):867-78
references: 10579577
references: Pharmacol Ther. 1994;64(3):445-75
references: 7724657
references: Clin Exp Pharmacol Physiol. 2001 Jan-Feb;28(1-2):95-9
references: 11153547
references: Neuropharmacology. 1992 Jun;31(6):585-92
references: 1407398
references: J Physiol. 1999 Jan 15;514 ( Pt 2):351-67
references: 9852319
references: J Auton Nerv Syst. 1987 Jul;20(1):73-86
references: 2443549
references: Histochem Cell Biol. 2009 Jan;131(1):29-41
references: 18787835
references: Clin Exp Pharmacol Physiol. 2005 May-Jun;32(5-6):467-72
references: 15854160
references: Am J Physiol. 1989 Jun;256(6 Pt 2):R1325-30
references: 2567578
references: Am J Physiol Regul Integr Comp Physiol. 2003 Nov;285(5):R1231-9
references: 12881200
references: Acta Physiol Scand. 2003 Jan;177(1):37-42
references: 12492777
references: Exp Physiol. 2011 Mar;96(3):262-74
references: 21148626
references: J Physiol. 1998 Dec 1;513 ( Pt 2):521-30
references: 9807000
references: Am J Physiol Regul Integr Comp Physiol. 2004 Nov;287(5):R1164-71
references: 15231493
references: Neuroscience. 1999;88(3):949-57
references: 10363830
references: Mol Med Today. 1999 May;5(5):216-24
references: 10322314
references: Brain Res. 2005 Jan 25;1032(1-2):85-93
references: 15680945
references: Brain Res. 2001 Mar 16;894(2):233-40
references: 11251196
references: Neuroscience. 2003;121(2):411-9
references: 14521999
references: J Auton Nerv Syst. 1999 May 28;76(2-3):118-26
references: 10412835
references: Auton Neurosci. 2010 Dec 8;158(1-2):79-85
references: 20655811
references: Pharmacol Rev. 1998 Sep;50(3):413-92
references: 9755289
references: Hypertension. 2005 Aug;46(2):341-8
references: 16027241
references: Physiol Rev. 2007 Apr;87(2):659-797
references: 17429044
references: Exp Physiol. 2006 Mar;91(2):403-11
references: 16299016
references: J Neurosci. 2003 Aug 13;23(19):7426-37
references: 12917379
references: Neuroscience. 2003;118(3):585-601
references: 12710969
references: J Neurosci Methods. 1980 Dec;3(2):129-49
references: 6110810
references: J Cell Physiol. 2008 Oct;217(1):155-61
references: 18481265
references: J Physiol. 2011 Sep 15;589(Pt 18):4457-71
references: 21708906
references: Clin Exp Pharmacol Physiol. 1998 Jun;25(6):461-3
references: 9673825
references: Brain Res. 1998 Aug 10;801(1-2):239-43
references: 9729407
references: Brain Res. 2010 Jul 16;1344:87-95
references: 20478280
references: Hypertension. 2002 Feb;39(2):275-80
references: 11847197
references: Physiol Rev. 2002 Oct;82(4):1013-67
references: 12270951
references: Clin Exp Pharmacol Physiol. 2005 May-Jun;32(5-6):419-25
references: 15854152
references: Nat Rev Neurosci. 2006 May;7(5):335-46
references: 16760914
references: Clin Exp Hypertens. 1997 Oct;19(7):1117-34
references: 9310207
references: Br J Pharmacol. 2005 Jun;145(3):342-52
references: 15735655
references: Am J Physiol. 1994 Jan;266(1 Pt 2):R306-13
references: 8304554
references: Eur J Neurosci. 1998 Dec;10(12):3898-902
references: 9875366
references: J Physiol. 2002 Jul 15;542(Pt 2):529-36
references: 12122150
references: Am J Physiol. 1998 Sep;275(3):R728-34
references: 9728069
references: Physiol Rev. 1994 Apr;74(2):323-64
references: 8171117
references: J Comp Neurol. 1982 Mar 1;205(3):260-72
references: 6122696
references: Am J Physiol Heart Circ Physiol. 2000 Jun;278(6):H2057-68
references: 10843905
references: Brain Res. 1988 Jun 28;454(1-2):123-30
references: 2900661
references: J Physiol. 2006 Oct 15;576(Pt 2):569-83
references: 16873404
references: J Neuroendocrinol. 2006 Apr;18(4):266-72
references: 16503921
references: Brain Res. 1994 Apr 4;641(2):249-56
references: 8012826
references: J Neurosci Res. 2009 Jul;87(9):2066-77
references: 19229989
references: J Neurosci. 2000 Dec 1;20(23):8868-75
references: 11102496
references: J Physiol. 2007 Jun 15;581(Pt 3):1129-45
references: 17395636