Juan F Lopez-Gimenez

Juan F Lopez-Gimenez
Spanish National Research Council | CSIC · Institute of Parasitology and Biomedicine "Lopez-Neyra"

PhD

About

52
Publications
5,888
Reads
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3,622
Citations
Citations since 2017
11 Research Items
1111 Citations
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2017201820192020202120222023050100150200
2017201820192020202120222023050100150200
2017201820192020202120222023050100150200
Additional affiliations
September 2016 - July 2018
University of Santiago de Compostela
Position
  • Researcher
January 2016 - July 2016
Virginia Commonwealth University
Position
  • Professor
January 2004 - December 2010
University of Glasgow

Publications

Publications (52)
Article
Antipsychotic drugs remain the current standard for schizophrenia treatment. Although they directly recognize the orthosteric binding site of numerous monoaminergic G protein-coupled receptors (GPCRs), these drugs, and particularly second-generation antipsychotics such as clozapine, all have in common a very high affinity for the serotonin 5-HT2A r...
Article
The 5-HT2A receptor is a homodimeric G protein-coupled receptor implied in multiple diseases, including schizophrenia. Recently, its co-crystallisation with the antipsychotic drugs zotepine and risperidone has revealed the importance of its extracellular domains in its pharmacology. Previous studies have shown that the non-specific disruption of ex...
Preprint
Full-text available
Sp8 and Sp6 are two closely related Sp genes expressed in the limb ectoderm where they regulate proximo-distal and dorso-ventral patterning. Mouse genetics revealed that they act together in a dose-dependent manner but with Sp8 making a much greater contribution. Here, we combine ChIP-seq and RNA-seq genome-wide analyses to investigate the Sp8 regu...
Article
Full-text available
A better understanding of the molecular mechanisms that participate in the development and clinical manifestations of schizophrenia can lead to improve our ability to diagnose and treat this disease. Previous data strongly associated the levels of deregulated ADAMTS2 expression in peripheral blood mononuclear cells (PBMCs) from patients at first ep...
Article
Oxidative stress (OxS) is involved in the development of cell injures occurring in retinal diseases while Poly(ADP-ribose) Polymerase-1 (PARP-1) is a key protein involved in the repair of the DNA damage caused by OxS. Inhibition of PARP-1 activity with the pharmacological inhibitor PJ34 in mouse retinal explants subjected to H2O2-induced oxidative...
Article
Full-text available
Current drug discovery procedures require fast and effective quantification of the pharmacological response evoked in living cells by agonist compounds. In the case of G-protein coupled receptors (GPCRs), the efficacy of a particular drug to initiate the endocytosis process is related to the formation of endocytic vesicles or endosomes and their su...
Article
Morphine and related opioids are the mainstay of analgesic treatment, especially in patients suffering chronic pain. Besides their antinociceptive effects they may also exhibit anxiolytic-like properties that could contribute to pain relief. The pharmacological manipulation of the serotonergic system may not only modulate pain transmission and proc...
Article
Antipsychotic drugs remain the standard for schizophrenia treatment. Despite their effectiveness in treating hallucinations and delusions, prolonged exposure to antipsychotic medications leads to cognitive deficits in both schizophrenia patients and animal models. The molecular mechanisms underlying these negative effects on cognition remain to be...
Chapter
The neuropsychological effects of naturally occurring psychoactive chemicals have been recognized for millennia. Hallucinogens, which include naturally occurring chemicals such as mescaline and psilocybin, as well as synthetic compounds, such as lysergic acid diethylamide (LSD), induce profound alterations of human consciousness, emotion, and cogni...
Article
Morphine inefficiency to induce the internalization of mu opioid (MOP) receptors observed in numerous experimental models constitutes a paradigm of G-protein coupled receptor (GPCR) functional selectivity. We recently described that activation of Gαq/11 proteins through 5-HT2A serotonin receptors co-expressed in the same cells facilitates MOP recep...
Article
Full-text available
Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) can form multiprotein complexes (heteromers), which can alter the pharmacology and functions of the constituent receptors. Previous findings demonstrated that the Gq/11-coupled serotonin 5-HT2A receptor and the Gi/o-coupled metabotropic glutamate 2 (mGlu2) recep...
Article
Full-text available
The activation of G-protein coupled receptors by agonist compounds results in diverse biological responses in cells, such as the endocytosis process consisting in the translocation of receptors from the plasma membrane to the cytoplasm within internalizing vesicles or en-dosomes. In order to functionally evaluate endocytosis events resulted from ph...
Article
Earlier autoradiographic studies with the 5-HT2 receptor agonist [125I](±)DOI in human brain showed unexpected biphasic competition curves for various 5-HT2A antagonists. We have performed similar studies in rat brain regions with selective 5-HT2A (M100907) and 5-HT2C (SB242084) antagonists together with ketanserin and mesulergine. The effect of GT...
Article
Full-text available
Serotonin and glutamate G protein-coupled receptor (GPCR) neurotransmission affects cognition and perception in humans and rodents. GPCRs are capable of forming heteromeric complexes that differentially alter cell signaling, but the role of this structural arrangement in modulating behavior remains unknown. Here we identified three residues located...
Article
Yohimbine has been shown to modulate the pharmacological actions of opioid drugs in a way that could be of potential therapeutic interest. This work tries to study if this interaction involves the impairment of opioid receptor activation at the cellular level by studying the effects of morphine and yohimbine on NG108-15 neuroblastoma x glioma hybri...
Article
Full-text available
Internalisation of the mu opioid receptor from the surface of cells is generally achieved by receptor occupancy with agonist ligands of high efficacy. However, in many situations the potent analgesic morphine fails to promote internalisation effectively and whether there is a direct link between this and the propensity for the sustained use of morp...
Article
Full-text available
The serotonin (5-hydroxytryptamine; 5-HT) 2A receptor is a cell surface class A G protein-coupled receptor that regulates a multitude of physiological functions of the body and is a target for antipsychotic drugs. Here we found by means of fluorescence resonance energy transfer and immunoprecipitation studies that the 5-HT(2A)-receptor homodimerize...
Article
Full-text available
Many G-protein-coupled receptors, including the alpha(1b)-adrenoceptor, form homo-dimers or oligomers. Mutation of hydrophobic residues in transmembrane domains I and IV alters the organization of the alpha(1b)-adrenoceptor oligomer, with transmembrane domain IV playing a critical role. These mutations also result in endoplasmic reticulum trapping...
Article
Full-text available
Analysis of the distribution of mRNA encoding the serotonin (5-hydroxytryptamine) 5-HT(2A) receptor and the mu opioid peptide receptor in rat brain demonstrated their coexpression in neurons in several distinct regions. These regions included the periaqueductal gray, an area that plays an important role in morphine-induced analgesia but also in the...
Chapter
Full-text available
Serotonin (5-hydroxytryptamine [5-HT]) produces its effects through a variety of membrane-bound receptors, located in the central and peripheral nervous systems and in non-neuronal tissues in the gastrointestinal tract, cardiovascular system, and blood. The knowledge of the anatomical localization of the receptors is an important step forward for t...
Article
Full-text available
The psychosis associated with schizophrenia is characterized by alterations in sensory processing and perception. Some antipsychotic drugs were identified by their high affinity for serotonin 5-HT2A receptors (2AR). Drugs that interact with metabotropic glutamate receptors (mGluR) also have potential for the treatment of schizophrenia. The effects...
Article
Full-text available
Approaches to identify G protein-coupled receptor oligomers rather than dimers have been lacking. Using concatamers of fluorescent proteins, we established conditions to monitor sequential three-color fluorescence resonance energy transfer (3-FRET) and used these to detect oligomeric complexes of the alpha(1b)-adrenoceptor in single living cells. M...
Article
The structural basis of the quaternary organization of rhodopsin has recently been explored and modeled. Because information obtained from studying rhodopsin has frequently been directly applicable to other G protein-coupled receptors we wished to ascertain if dimeric and/or oligomeric forms of the alpha(1b)-adrenoceptor could be observed and if so...
Article
Full-text available
The functional role of heteromers of G-protein-coupled receptors is a matter of debate. In the present study, we demonstrate that heteromerization of adenosine A1 receptors (A1Rs) and A2A receptors (A2ARs) allows adenosine to exert a fine-tuning modulation of glutamatergic neurotransmission. By means of coimmunoprecipitation, bioluminescence and ti...
Article
A wide range of techniques have been employed to examine the quaternary structure of G-protein-coupled receptors (GPCRs). Although it is well established that homo-dimerisation is common, recent studies have sought to explore the physical basis of these interactions and the role of dimerisation in signal transduction. Growing evidence hints at the...
Article
It is now well established that rhodopsin-like, family-A G protein-coupled receptors (GPCRs) can exist within homo- and heterodimeric/oligomeric complexes. However, limited information is currently available on the molecular basis of these interactions or their selectivity. Using the alpha1-adrenoceptor family as a model, this has been examined usi...
Article
It is now well established that rhodopsin-like, family-AG protein-coupled receptors (GPCRs) can exist within homo- and heterodimeric/oligomeric complexes. However, limited information is currently available on the molecular basis of these interactions or their selectivity. Using the alpha(1)-adrenoceptor family as a model, this has been examined us...
Article
Full-text available
Three distinct genes encode alpha(1)-adrenoceptors. Although homodimers of each subtype have been reported, certain but not all combinations of heterodimers of the alpha(1)-adrenoceptors appear to form. Key studies in this field are reviewed and the approaches that have been applied to monitoring the selectivity and the basis of alpha(1)-adrenocept...
Article
Full-text available
Combinations of coimmunoprecipitation, single-cell fluorescence resonance energy transfer, and cell-surface time-resolved fluorescence resonance energy transfer demonstrated protein-protein interactions and quaternary structure for the alpha(1b)-adrenoceptor. Self-association of transmembrane domain 1 and its interaction with the full-length recept...
Article
Full-text available
G-protein-coupled receptors (GPCRs) represent the largest family of receptors involved in transmembrane signaling. Although these receptors were generally believed to be monomeric entities, accumulating evidence supports the presence of GPCRs in multimeric forms. Here, using immunoprecipitation as well as time-resolved fluorescence resonance energy...
Article
Full-text available
Using combinations of bioluminescence resonance energy transfer, time-resolved fluorescence resonance energy transfer and the functional complementation of pairs of inactive receptor-G protein fusion proteins, the human alpha(1A-1)-adrenoceptor was shown to form homodimeric/oligomeric complexes when expressed in human embryonic kidney (HEK) 293 cel...
Article
G protein-coupled receptors can exist as dimers and/or higher order oligomers. Such quaternary structure appears central to their plasma membrane delivery and, potentially, to function. Recent evidence that these receptors can form hetero- as well as homo-dimers/oligomers has significant implications for pharmacology and pathophysiology. Knowledge...
Article
Human D2Long (D2L) and D2Short (D2S) dopamine receptor isoforms were modified at their N-terminus by the addition of a human immunodeficiency virus (HIV) or a FLAG epitope tag. The receptors were then expressed in Spodoptera frugiperda 9 (Sf9) cells using the baculovirus system, and their oligomerization was investigated by means of co-immunoprecip...
Article
A dopamine D(2Short) receptor:G(alphao) fusion protein was expressed in Sf9 cells using the baculovirus expression system. [(3)H]Spiperone bound to D(2Short):G(alphao) with a pK(d) approximately 10. Dopamine stimulated the binding of [(35)S]guanosine-5'-O-(3-thio)triphosphate (GTPgammaS) to D(2Short):G(alphao) expressed with Gbeta(1)gamma(2) (E(max...
Article
There is increasing evidence that G protein-coupled receptors (GPCRs) may form homo- or hetero-oligomers and that this may be important for their function. Evidence in favor of oligomerization comes from biochemical studies, studies of functional complementation and recent studies using energy transfer techniques, which provide direct evidence for...
Article
Quantitative receptor autoradiography was used to study possible alterations of the densities of multiple serotonin (5-HT) receptor subtypes and of serotonin transporter in the brain of 5-HT(2C) receptor knockout mice. The radioligands employed were [(3)H]citalopram, [(3)H]WAY100,635, [(3)H]8-OH-DPAT, [(3)H]GR125743, [(3)H]sumatriptan, [(3)H]MDL100...
Article
Quantitative receptor autoradiography was used to study possible alterations of the densities of multiple serotonin (5-HT) receptor subtypes and of serotonin transporter in the brain of 5-HT2C receptor knockout mice. The radioligands employed were [3H]citalopram, [3H]WAY100,635, [3H]8-OH-DPAT, [3H]GR125743, [3H]sumatriptan, [3H]MDL100,907, [125I](±...
Article
We have expanded previous studies with the 5-hydroxytryptamine (5-HT)(2) receptor agonist (+/-)-1-(2,5-dimethoxy-4-[(125)I]iodophenyl)-2-aminopropane [(+/-)-[(125)I]DOI] in human brain that had shown biphasic competition curves for several 5-HT(2A) receptor antagonists by using new selective antagonists of 5-HT(2A) (MDL100,907) and 5-HT(2C) (SB2420...
Article
The distribution of serotonin 5-HT2C receptor mRNA in monkey brain was studied by in situ hybridization and compared with the distribution of [3H]mesulergine binding sites as visualized by receptor autoradiography. 5-HT2C receptor transcripts showed a widespread and heterogeneous distribution. The strongest hybridization signal was detected in chor...
Article
The anatomic distribution of serotonin 5-HT2A receptors visualized with [3H]MDL100,907 and of their mRNA detected by in situ hybridization were studied in monkey brain. Both autoradiographic patterns of signal showed heterogeneous distributions and were in general in good agreement in the majority of brain regions. In most neocortical areas, [3H]MD...
Article
Abstract 5-HT2A receptors have been visualized with [3H]MDL100,907 in selected human brain areas by autoradiography. These areas included caudate and putamen, nucleus dentatus of the cerebellum, substantia nigra, nucleus raphe dorsalis, locus coeruleus and inferior olive. In the striatum [3H]MDL100,907 labelling was compared with the pattern obtain...
Article
The selective antagonist for the 5-HT2A serotonin receptor MDL 100,907, recently characterized autoradiographically in rat brain, has been characterized as a radioligand for the visualization of this receptor in human and monkey brain. In both species [3H]MDL 100,907 binding to brain sections was saturable, had sub-nanomolar affinity (Kd = 0.14-0.1...
Article
The distribution of 5-HT1A receptor mRNA in the human brain was studied in neonatal, children and adult cases by means of in situ hybridization histochemistry, using an oligonucleotide derived from the coding region of the human receptor. A prenatal pattern of development was observed. The hippocampus, raphe nuclei and neocortex presented high leve...
Article
Full-text available
The recently developed 5-HT2A receptor selective antagonist [3H]MDL100,907 ((+/-)2,3-dimethoxyphenyl-1-[2-(4-piperidine)-methanol]) has been characterized as a radioligand for the autoradiographic visualization of these receptors. [3H]MDL100,907 binding to rat brain tissue sections was saturable, had sub-nanomolar affinity (Kd = 0.2-0.3 nM), and pr...
Article
We have found that the distribution of 5-HT1A receptors in monkey brain, labelled with the agonist3H-8-OH-DPAT and the antagonist3H-WAY 100635 was very similar at the levels examined, and corresponded well with that observed for the cells containing mRNA coding for this receptor, confirming the somatodendritic localization of 5-HT1A receptors in mo...
Article
The serotonin (5-hydroxytryptamine, or 5-HT) 2A receptor is a cell surface class A G protein-coupled receptor that regulates a multitude of physiological functions of the body, and is a target for antipsychotic drugs. Here we found by means of FRET and immunoprecipitation studies that the 5-HT<sub>2A</sub>-receptor homo-dimerized in live cells, whi...
Article
Analysis of the distribution of mRNA encoding the 5-HT<sub>2A</sub> receptor and the mu opioid peptide receptor in rat brain demonstrated their co-expression in neurones in a number of distinct regions. These included the periacqueductal grey, an area that plays an important role in morphine-induced analgesia but also in the development of toleranc...

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Question
We are attempting to conduct studies of stress fiber formation response assessed by fluorescent phalloidin staining upon activation of heterologous expressed receptors in HEK293 cells. We would like to know whether these cells are a good choice for this sort of study and if not, which cellular phenotype would be a better alternative.

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