title: Rapid Glucocorticoid-Induced Activation of TRP and CB1 Receptors Causes Biphasic Modulation of Glutamate Release in Gastric-Related Hypothalamic Preautonomic Neurons.
abstract: Glucocorticoids rapidly regulate synaptic input to neuroendocrine cells in the hypothalamic paraventricular nucleus (PVN) by inducing the retrograde release of endogenous messengers. Here we investigated the rapid effects of dexamethasone (DEX) on excitatory synaptic input to feeding-related, preautonomic PVN neurons using whole-cell patch-clamp recordings. In ∼50% of identified gastric-related preautonomic PVN neurons, DEX elicited a biphasic synaptic response characterized by an initial rapid and transient increase in the frequency of miniature excitatory postsynaptic currents (mEPSCs), followed by a decrease in mEPSC frequency within 9 min; remaining cells displayed only a decrease in mEPSC frequency. The late-phase decrease in mEPSC frequency was mimicked by the cannabinoid receptor agonists anandamide (AEA) and WIN 55,212-2, and it was blocked by the CB1 receptor antagonist AM251. The biphasic DEX effect was mimicked by AEA. The early increase in mEPSCs was mimicked by activation of transient receptor potential vanilloid type 1 (TRPV1) receptors with capsaicin and by activation of TRPV4 receptors with 4-α-PDD. The increase was reduced, but not blocked, by selective TRPV1 antagonists and in TRPV1 knockout mice; it was blocked completely by the broad-spectrum TRPV antagonist ruthenium red and by combined application of selective TRPV1 and TRPV4 antagonists. The DEX effects were prevented entirely by intracellular infusion of the G-protein inhibitor, GDPβS. Thus, DEX biphasically modulates synaptic glutamate onto a subset of gastric-related PVN neurons, which is likely mediated by induction of a retrograde messenger. The effect includes a TRPV1/4 receptor-mediated transient increase and subsequent CB1 receptor-mediated suppression of glutamate release. Multiphasic modulation of glutamate input to PVN neurons represents a previously unappreciated complexity of control of autonomic output by glucocorticoids and endogenous cannabinoids.
authors: Department of Physiology, University of Kentucky College of Medicine Lexington, KY, USA.
authors: Carie R
authors: CR
authors: Boychuk
authors: Andrea
authors: A
authors: Zsombok
authors: Jeffrey G
authors: JG
authors: Tasker
authors: Bret N
authors: BN
authors: Smith
keywords: cannabinoid; paraventricular nucleus; vanilloid
references: Diabetes. 2012 Jun;61(6):1381-90
references: 22492526
references: Am J Physiol Regul Integr Comp Physiol. 2009 Feb;296(2):R454-66
references: 19091909
references: Endocrinology. 2007 Apr;148(4):1868-81
references: 17194747
references: Am J Physiol Renal Physiol. 2006 Jan;290(1):F117-26
references: 16091583
references: J Biol Chem. 2000 Jan 28;275(4):2756-62
references: 10644739
references: Br J Pharmacol. 2000 Jan;129(2):227-30
references: 10694225
references: J Physiol. 2000 Feb 15;523 Pt 1:193-209
references: 10673555
references: Am J Physiol Regul Integr Comp Physiol. 2006 Sep;291(3):R518-29
references: 16690776
references: Trends Endocrinol Metab. 2003 Nov;14(9):394-6
references: 14580755
references: Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):396-401
references: 14691263
references: Naunyn Schmiedebergs Arch Pharmacol. 1982 Sep;320(3):205-16
references: 6182473
references: Neuroscience. 2006;139(4):1405-15
references: 16603318
references: Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9264-9
references: 10922076
references: Brain Res. 1993 Jun 18;614(1-2):197-204
references: 8348312
references: Am J Physiol Regul Integr Comp Physiol. 2007 Jan;292(1):R64-76
references: 16973931
references: Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3655-60
references: 10725386
references: Endocrinology. 2005 Oct;146(10):4292-301
references: 15994343
references: Pflugers Arch. 2005 Oct;451(1):143-50
references: 15971082
references: Neuroreport. 1998 Jun 22;9(9):2045-8
references: 9674591
references: Nature. 1999 Jul 29;400(6743):452-7
references: 10440374
references: J Neurosci. 2004 May 19;24(20):4709-17
references: 15152030
references: J Neurosci. 2002 Aug 1;22(15):6408-14
references: 12151520
references: J Physiol. 2001 Nov 15;537(Pt 1):161-77
references: 11711570
references: EMBO J. 2005 Sep 7;24(17):3026-37
references: 16107881
references: Eur J Neurosci. 2007 May;25(9):2773-82
references: 17459108
references: Nature. 2003 Jul 24;424(6947):434-8
references: 12879072
references: J Comp Neurol. 2001 Oct 8;439(1):1-18
references: 11579378
references: J Neurosci. 2003 Jun 15;23(12):4850-7
references: 12832507
references: J Neurosci. 2011 Sep 28;31(39):14024-31
references: 21957263
references: J Neurophysiol. 2007 Sep;98(3):1591-9
references: 17615134
references: Sci STKE. 2001 Jul 10;2001(90):re1
references: 11752662
references: Nat Neurosci. 2006 Jan;9(1):93-8
references: 16327782
references: J Comp Neurol. 2004 Jun 14;474(1):24-42
references: 15156577
references: J Neurosci. 2003 Apr 15;23(8):3136-44
references: 12716921
references: J Neurosci. 2006 Sep 20;26(38):9666-72
references: 16988037
references: J Virol. 2007 Oct;81(19):10742-57
references: 17652377
references: J Neurophysiol. 2001 Jan;85(1):435-8
references: 11152744
references: Prog Brain Res. 2008;170:379-88
references: 18655897
references: Neuroendocrinology. 2003 Dec;78(6):294-300
references: 14688442
references: J Neurosci. 2009 Jan 14;29(2):393-401
references: 19144839
references: J Neurophysiol. 2004 Sep;92(3):1807-16
references: 15115794
references: J Neuroendocrinol. 2002 Dec;14(12):929-32
references: 12472873
references: Nature. 1994 Dec 15;372(6507):686-91
references: 7990962
references: Endocrinology. 2010 Oct;151(10):4811-9
references: 20702575
references: Physiol Rev. 2007 Jan;87(1):165-217
references: 17237345
references: Eur J Biochem. 2004 May;271(10):1827-34
references: 15128293
references: J Neurosci. 2003 May 1;23(9):3844-54
references: 12736355
references: J Comp Neurol. 1980 Dec 1;194(3):555-70
references: 7451682
references: Curr Opin Nephrol Hypertens. 2007 Sep;16(5):451-8
references: 17693761
references: Pflugers Arch. 2003 Jun;446(3):298-303
references: 12715179
references: J Physiol. 2004 Sep 15;559(Pt 3):923-38
references: 15272041
references: Physiol Behav. 1989 Aug;46(2):265-71
references: 2574890
references: J Physiol. 2006 Jun 1;573(Pt 2):395-412
references: 16581866
references: Neuropharmacology. 1977 Jul-Aug;16(7-8):533-6
references: 917261
references: J Physiol. 2005 Dec 15;569(Pt 3):751-60
references: 16239276
references: J Auton Nerv Syst. 2000 Mar 15;79(2-3):117-28
references: 10699642
references: J Comp Neurol. 2003 Sep 29;464(4):525-39
references: 12900922
references: Nat Neurosci. 2008 Feb;11(2):152-9
references: 18204441
references: Behav Brain Res. 1986 Dec;22(3):265-81
references: 3098259
references: Microsc Res Tech. 1999 Aug 15-Sep 1;46(4-5):296-304
references: 10469465
references: Brain Res. 2005 May 10;1043(1-2):1-11
references: 15862512
references: J Neurosci. 2006 Aug 30;26(35):9069-75
references: 16943565