The Existence of FGFR1–5-HT1A Receptor Heterocomplexes in Midbrain 5-HT Neurons of the Rat: Relevance for Neuroplasticity

Borroto‐Escuela, Dasiel O.; Romero-Fernández, Wilber; Pérez-Alea, Mileidys; Narváez, Manuel; Tarakanov, Alexander O.; Mudò, Giuseppa; Agnati, Luigi F.; Ciruela, Francisco; Belluardo, Natale

doi:10.1523/jneurosci.4203-11.2012

Cited by 18 publications

(20 citation statements)

References 35 publications

(41 reference statements)

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“…More recently, FGFR1 has also been shown to heterodimerize with the 5-HT1A receptor in both the hippocampus and the raphe (Borroto-Escuela et al, 2012a; Borroto-Escuela et al, 2012b). The heteroreceptor complex has been co-immunoprecipitated in cultured cells, and in neurons in the dorsal rat hippocampal formation and in the dorsal raphe.…”

Section: Affective Functions Of the Fgf Systemmentioning

confidence: 99%

“…Moreover, the investigators co-administered FGF2 and serotonin and uncovered a heightened response in an antidepressant test, as compared to the effect of either ligand alone. Moreover, combining FGF-2 and 5-HT1A agonist synergistically enhanced both receptor signaling and cell differentiation, suggesting a trophic role in the serotonergic neurons (Borroto-Escuela et al, 2012b). Given the large literature on 5HT1A receptor signaling (Hannon and Hoyer, 2008), and its role in mediating the mode of action of antidepressants and in the regulation of emotional responsiveness (Blier and Abbott, 2001; Blier and Ward, 2003), the molecular interaction between these two systems opens up exciting avenues for understanding the biology and pathophysiology of affect and mood.…”

Section: Affective Functions Of the Fgf Systemmentioning

confidence: 99%

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The Fibroblast Growth Factor Family: Neuromodulation of Affective Behavior

Turner

Watson

Akil

2012

Neuron

138

126

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In this review we propose a broader view of the role of the fibroblast growth factor (FGF) family in modulating brain function. We suggest that some of the FGF ligands together with the FGF receptors are altered in individuals with affective disorder and modulate emotionality in animal models. Thus, we propose that members of the FGF family may be genetic predisposing factors for anxiety, depression or substance abuse; that they play a key organizing role during early development but continue to play a central role in neuroplasticity in adulthood; and that they work not only over extended time frames, but also via rapid signaling mechanisms, allowing them to exert an “on-line” influence on behavior. Therefore, the FGF family appears to be a prototype of “switch genes” that are endowed with organizational and modulatory properties across the lifespan, and that may represent molecular candidates as biomarkers and treatment targets for affective and addictive disorders.

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Section: Affective Functions Of the Fgf Systemmentioning

confidence: 99%

Section: Affective Functions Of the Fgf Systemmentioning

confidence: 99%

The Fibroblast Growth Factor Family: Neuromodulation of Affective Behavior

Turner

Watson

Akil

2012

Neuron

138

126

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“…With the in situ PLA method the striatal adenosine 2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromers and D2R-oxytocin receptor heteromers have for example, been shown [35, 39]. Also the hippocampal and the mesencephalic raphe FGFR1-5-HT1AR heteromers have recently been demonstrated [36, 37]. The in situ PLA procedure represents a high selectivity and sensitivity assay to demonstrate GPCR heteromers in brain [38].…”

Section: The Receptor-receptor Interaction Toolboxmentioning

confidence: 99%

On the G-Protein-Coupled Receptor Heteromers and Their Allosteric Receptor-Receptor Interactions in the Central Nervous System: Focus on Their Role in Pain Modulation

Borroto-Escuela

Romero-Fernández

Rivera

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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The modulatory role of allosteric receptor-receptor interactions in the pain pathways of the Central Nervous System and the peripheral nociceptors has become of increasing interest. As integrators of nociceptive and antinociceptive wiring and volume transmission signals, with a major role for the opioid receptor heteromers, they likely have an important role in the pain circuits and may be involved in acupuncture. The delta opioid receptor (DOR) exerts an antagonistic allosteric influence on the mu opioid receptor (MOR) function in a MOR-DOR heteromer. This heteromer contributes to morphine-induced tolerance and dependence, since it becomes abundant and develops a reduced G-protein-coupling with reduced signaling mainly operating via β-arrestin2 upon chronic morphine treatment. A DOR antagonist causes a return of the Gi/o binding and coupling to the heteromer and the biological actions of morphine. The gender- and ovarian steroid-dependent recruitment of spinal cord MOR/kappa opioid receptor (KOR) heterodimers enhances antinociceptive functions and if impaired could contribute to chronic pain states in women. MOR1D heterodimerizes with gastrin-releasing peptide receptor (GRPR) in the spinal cord, mediating morphine induced itch. Other mechanism for the antinociceptive actions of acupuncture along meridians may be that it enhances the cross-desensitization of the TRPA1 (chemical nociceptor)-TRPV1 (capsaicin receptor) heteromeric channel complexes within the nociceptor terminals located along these meridians. Selective ionotropic cannabinoids may also produce cross-desensitization of the TRPA1-TRPV1 heteromeric nociceptor channels by being negative allosteric modulators of these channels leading to antinociception and antihyperalgesia.

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“…In situ PLA have the potential to enable a fuller understanding of GPCR receptor–receptor and could be highly suited to investigate GPCR heteromers in tissue, providing new insights in basic biological mechanisms, heteroreceptor levels and their locations, e.g., in the brain (Borroto-Escuela et al, 2012). …”

Section: Receptor Heteromers and Their Allosteric Receptor–receptor Imentioning

confidence: 99%

On the existence and function of galanin receptor heteromers in the central nervous system

Fuxé¹,

Borroto‐Escuela²,

Romero-Fernández³

et al. 2012

Front. Endocrin.

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Galanin receptor (GalR) subtypes 1–3 linked to central galanin neurons may form heteromers with each other and other types of G protein-coupled receptors in the central nervous system (CNS). These heteromers may be one molecular mechanism for galanin peptides and their N-terminal fragments (gal 1-15) to modulate the function of different types of glia–neuronal networks in the CNS, especially the emotional and the cardiovascular networks. GalR–5-HT1A heteromers likely exist with antagonistic GalR–5-HT1A receptor–receptor interactions in the ascending midbrain raphe 5-HT neuron systems and their target regions. They represent a novel target for antidepressant drugs. Evidence is given for the existence of GalR1–5-HT1A heteromers in cellular models with trans-inhibition of the protomer signaling. A GalR1–GalR2 heteromer is proposed to be a galanin N-terminal fragment preferring receptor (1-15) in the CNS. Furthermore, a GalR1–GalR2–5-HT1A heterotrimer is postulated to explain why only galanin (1-15) but not galanin (1-29) can antagonistically modulate the 5-HT1A receptors in the dorsal hippocampus rich in gal fragment binding sites. The results underline a putative role of different types of GalR–5-HT1A heteroreceptor complexes in depression. GalR antagonists may also have therapeutic actions in depression by blocking the antagonistic GalR–NPYY1 receptor interactions in putative GalR–NPYY1 receptor heteromers in the CNS resulting in increases in NPYY1 transmission and antidepressant effects. In contrast the galanin fragment receptor (a postulated GalR1–GalR2 heteromer) appears to be linked to the NPYY2 receptor enhancing the affinity of the NPYY2 binding sites in a putative GalR1–GalR2–NPYY2 heterotrimer. Finally, putative GalR–α2-adrenoreceptor heteromers with antagonistic receptor–receptor interactions may be a widespread mechanism in the CNS for integration of galanin and noradrenaline signals also of likely relevance for depression.

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The Existence of FGFR1–5-HT1A Receptor Heterocomplexes in Midbrain 5-HT Neurons of the Rat: Relevance for Neuroplasticity

Cited by 18 publications

References 35 publications

The Fibroblast Growth Factor Family: Neuromodulation of Affective Behavior

The Fibroblast Growth Factor Family: Neuromodulation of Affective Behavior

On the G-Protein-Coupled Receptor Heteromers and Their Allosteric Receptor-Receptor Interactions in the Central Nervous System: Focus on Their Role in Pain Modulation

On the existence and function of galanin receptor heteromers in the central nervous system

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