title: Dopamine-galanin receptor heteromers modulate cholinergic neurotransmission in the rat ventral hippocampus.
abstract: Previous studies have shown that dopamine and galanin modulate cholinergic transmission in the hippocampus, but little is known about the mechanisms involved and their possible interactions. By using resonance energy transfer techniques in transfected mammalian cells, we demonstrated the existence of heteromers between the dopamine D(1)-like receptors (D(1) and D(5)) and galanin Gal(1), but not Gal(2) receptors. Within the D(1)-Gal(1) and D(5)-Gal(1) receptor heteromers, dopamine receptor activation potentiated and dopamine receptor blockade counteracted MAPK activation induced by stimulation of Gal(1) receptors, whereas Gal(1) receptor activation or blockade did not modify D(1)-like receptor-mediated MAPK activation. Ability of a D(1)-like receptor antagonist to block galanin-induced MAPK activation (cross-antagonism) was used as a "biochemical fingerprint" of D(1)-like-Gal(1) receptor heteromers, allowing their identification in the rat ventral hippocampus. The functional role of D(1)-like-Gal receptor heteromers was demonstrated in synaptosomes from rat ventral hippocampus, where galanin facilitated acetylcholine release, but only with costimulation of D(1)-like receptors. Electrophysiological experiments in rat ventral hippocampal slices showed that these receptor interactions modulate hippocampal synaptic transmission. Thus, a D(1)-like receptor agonist that was ineffective when administered alone turned an inhibitory effect of galanin into an excitatory effect, an interaction that required cholinergic neurotransmission. Altogether, our results strongly suggest that D(1)-like-Gal(1) receptor heteromers act as processors that integrate signals of two different neurotransmitters, dopamine and galanin, to modulate hippocampal cholinergic neurotransmission.
authors: Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas and Department of Biochemistry and Molecular Biology, University of Barcelona, 08028 Barcelona, Spain.
authors: Estefanía
authors: E
authors: Moreno
authors: Sandra H
authors: SH
authors: Vaz
authors: Ning-Sheng
authors: NS
authors: Cai
authors: Carla
authors: C
authors: Ferrada
authors: César
authors: C
authors: Quiroz
authors: Sandeep Kumar
authors: SK
authors: Barodia
authors: Nadine
authors: N
authors: Kabbani
authors: Enric I
authors: EI
authors: Canela
authors: Peter J
authors: PJ
authors: McCormick
authors: Carme
authors: C
authors: Lluis
authors: Rafael
authors: R
authors: Franco
authors: Joaquim A
authors: JA
authors: Ribeiro
authors: Ana M
authors: AM
authors: Sebastião
authors: Sergi
authors: S
authors: Ferré
references: Cell. 2002 Oct 18;111(2):219-30
references: 12408866
references: Eur J Pharmacol. 1993 Mar 15;245(1):1-7
references: 7682961
references: Regul Pept. 2004 Oct 15;122(2):91-8
references: 15380926
references: Nat Chem Biol. 2009 Mar;5(3):131-4
references: 19219011
references: Brain Res. 2004 Mar 19;1001(1-2):60-71
references: 14972654
references: J Neurosci. 1995 Nov;15(11):7150-7
references: 7472469
references: Eur J Pharmacol. 2010 Jan 10;626(1):9-17
references: 19837050
references: Cell Mol Life Sci. 2008 Jun;65(12):1796-805
references: 18500647
references: J Neurochem. 1998 Mar;70(3):1088-93
references: 9489729
references: Brain Res. 2008 Jul 11;1219:19-25
references: 18539266
references: Cell Mol Life Sci. 2008 Jun;65(12):1872-9
references: 18500649
references: Trends Pharmacol Sci. 1994 Jul;15(7):264-70
references: 7940991
references: Eur J Pharmacol. 2003 Aug 8;474(2-3):137-40
references: 12921854
references: Neuropsychopharmacology. 2007 Nov;32(11):2249-59
references: 17356572
references: Trends Pharmacol Sci. 2005 Mar;26(3):131-7
references: 15749158
references: Trends Pharmacol Sci. 2000 Mar;21(3):109-17
references: 10689365
references: Cell Mol Life Sci. 2008 Jun;65(12):1813-9
references: 18500645
references: Nat Rev Drug Discov. 2002 Oct;1(10):808-20
references: 12360258
references: Synapse. 2000 Aug;37(2):125-45
references: 10881034
references: Ann N Y Acad Sci. 1998 Dec 21;863:342-63
references: 9928182
references: J Neurosci. 2004 Mar 24;24(12):2905-13
references: 15044529
references: Cell Mol Life Sci. 2008 Jun;65(12):1842-53
references: 18500641
references: Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18676-81
references: 20956312
references: Proc Natl Acad Sci U S A. 1987 Oct;84(20):7339-43
references: 2444980
references: Brain Res. 1985 Dec 23;360(1-2):130-8
references: 2416401
references: Brain Res Mol Brain Res. 1997 Dec 1;52(1):121-9
references: 9450684
references: Brain Res Mol Brain Res. 2000 Mar 29;76(2):336-40
references: 10762709
references: Br J Pharmacol. 2009 May;157(1):64-75
references: 19413572
references: Trends Neurosci. 2007 Sep;30(9):440-6
references: 17692396
references: Nature. 2000 Jan 20;403(6767):274-80
references: 10659839
references: Biochem J. 2011 Jan 1;433(1):11-8
references: 21158738
references: Hippocampus. 2010 Dec;20(12):1332-8
references: 20082290
references: Br J Pharmacol. 2009 Sep;158(1):5-14
references: 19309353
references: Neuropeptides. 1999 Jun;33(3):197-205
references: 10657492
references: J Neurosci Methods. 2001 Jul 15;108(1):71-83
references: 11459620
references: Neuroscience. 1986 Sep;19(1):223-40
references: 2431348
references: J Comp Neurol. 1999 Jul 5;409(3):469-81
references: 10379831
references: J Comp Neurol. 2004 Nov 22;479(4):410-23
references: 15514977
references: Brain Res Mol Brain Res. 1995 Dec 28;34(2):179-89
references: 8750821
references: Neuropsychopharmacology. 2004 Sep;29(9):1620-7
references: 15100705
references: J Pharmacol Exp Ther. 1996 May;277(2):775-83
references: 8627558
references: Pharmacol Ther. 2007 Aug;115(2):177-207
references: 17604107
references: J Neurosci. 2000 Aug 15;20(16):6276-81
references: 10934278
references: J Neurosci. 2006 Aug 16;26(33):8549-58
references: 16914681
references: Ann N Y Acad Sci. 1998 Dec 21;863:252-63
references: 9928176
references: J Comp Neurol. 1998 Apr 13;393(3):284-97
references: 9548550
references: Prog Mol Biol Transl Sci. 2010;91:41-52
references: 20691958
references: Neurosci Lett. 1996 Jul 5;212(1):21-4
references: 8823753
references: Life Sci. 1996;58(24):2185-99
references: 8649205
references: J Neurosci. 1986 Dec;6(12):3640-54
references: 2432203
references: Pharmacol Ther. 2008 Jun;118(3):359-71
references: 18486226