Principal Investigator:

Dr. Juan López Giménez, Científico Titular CSIC

Other personnel:

• David Ramos Melendro, técnico superior
• Sara Lucas Toca, estudiante en prácticas
• Arlet María Acanda de la Rocha, estudiante Máster

More information on group members

Research lines:

Our scientific research interests are focused on GPCR functioning from a molecular and cellular perspective, including all those aspects regarding receptor conformational changes after the binding of selective drugs, coupling of activated receptors to G proteins and/or other cellular effectors as well as the subsequent initiation of intracellular cascades of second messengers. In addition to cell signalling processes, we also investigate on those receptor-receptor interactions resulting in either homomeric as heteromeric new receptor complexes susceptible to present specific pharmacological profiles. The experimental approaches that we use essentially include molecular and cellular biology techniques, different mammalian cell heterologous expression models and in vitro biochemical and pharmacological assays. Another important aspect of our scientific research activity is the validation in physiological native systems of those findings previously observed by in vitro experimental approaches.

 Ongoing projects.

“In vivo validation of the pharmacological interactions of mu opioid and serotonin 5-HT_2A receptors: involvement in the development of morphine tolerance and dependence”.

We have previously described a pharmacological interaction between mu opioid and serotonin 5-HT_2A receptors resulting in the facilitation of mu opioid receptor internalisation by morphine after the parallel activation of 5-HT_2A receptors (Mol Pharmacol 74, 1278-1291 (2008)). At this moment we are investigating on the molecular and cellular mechanisms involved in this pharmacological interaction along with the effect of equivalent treatments in the development of morphine tolerance and dependence in experimental animal models.

 Collaborations.

Prof. Graeme Milligan. University of Glasgow.

Dr. Mabel Loza. Universidad de Santiago de Compostela.

Dr. Javier González-Maeso. Mount Sinai School of Medicine.

Dr. Teresa Vilaró. IIBB-CSIC.

Dr. Alvaro Díaz. IBBTEC-Universidad de Cantabria.

 

Funding:

Relevant publications (last 10 years)

Polanco MJ, López-Giménez JF, González-Martín C, Alguacil LF. Yohimbine does not affect opioid receptor activation but prevents adenylate cyclase regulation by morphine in NG108-15 cells. Life Sci. 2011 Jul 7.

 

Lopez-Gimenez JF, Milligan G. Opioid regulation of mu receptor internalisation: relevance to the development of tolerance and dependence. CNS Neurol Disord Drug Targets. 2010 Nov;9(5):616-26.

 

Brea J, Castro M, Giraldo J, López-Giménez JF, Padín JF, Quintián F, Cadavid MI, Vilaró MT, Mengod G, Berg KA, Clarke WP, Vilardaga JP, Milligan G, Loza MI. Evidence for distinct antagonist-revealed functional states of 5-hydroxytryptamine(2A) receptor homodimers. Mol Pharmacol. 2009 Jun;75(6):1380-91.

 

Canals M, Lopez-Gimenez JF, Milligan G. Cell surface delivery and structural re-organization by pharmacological chaperones of an oligomerization-defective alpha(1b)-adrenoceptor mutant demonstrates membrane targeting of GPCR oligomers. Biochem J. 2009 Jan 1;417(1):161-72.

 

Lopez-Gimenez JF, Vilaró MT, Milligan G. Morphine desensitization, internalization, and down-regulation of the mu opioid receptor is facilitated by serotonin 5-hydroxytryptamine2A receptor coactivation. Mol Pharmacol. 2008 Nov;74(5):1278-91.

 

González-Maeso J, Ang RL, Yuen T, Chan P, Weisstaub NV, López-Giménez JF, Zhou M, Okawa Y, Callado LF, Milligan G, Gingrich JA, Filizola M, Meana JJ, Sealfon SC. Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature. 2008 Mar 6;452(7183):93-7.

 

Milligan G, Canals M, Pediani JD, Ellis J, Lopez-Gimenez JF. The role of GPCR dimerisation/oligomerisation in receptor signalling. Ernst Schering Found Symp Proc. 2006;(2):145-61.

 

Lopez-Gimenez JF, Canals M, Pediani JD, Milligan G. The alpha1b-adrenoceptor exists as a higher-order oligomer: effective oligomerization is required for receptor maturation, surface delivery, and function. Mol Pharmacol. 2007 Apr;71(4):1015-29.

 

Milligan G, Pediani JD, Canals M, Lopez-Gimenez JF. Oligomeric structure of the alpha1b-adrenoceptor: comparisons with rhodopsin. Vision Res. 2006 Dec;46(27):4434-41.

 

Ciruela F, Casadó V, Rodrigues RJ, Luján R, Burgueño J, Canals M, Borycz J, Rebola N, Goldberg SR, Mallol J, Cortés A, Canela EI, López-Giménez JF, Milligan G, Lluis C, Cunha RA, Ferré S, Franco R. Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers. J Neurosci. 2006 Feb 15;26(7):2080-7.

 

Milligan G, Wilson S, López-Gimenez JF. The specificity and molecular basis of alpha1-adrenoceptor and CXCR chemokine receptor dimerization. J Mol Neurosci. 2005;26(2-3):161-8.

 

Milligan G, Pediani J, Fidock M, López-Giménez JF. Dimerization of alpha1-adrenoceptors. Biochem Soc Trans. 2004 Nov;32(Pt 5):847-50.

 

Carrillo JJ, López-Giménez JF, Milligan G. Multiple interactions between transmembrane helices generate the oligomeric alpha1b-adrenoceptor. Mol Pharmacol. 2004 Nov;66(5):1123-37.

 

Ramsay D, Carr IC, Pediani J, Lopez-Gimenez JF, Thurlow R, Fidock M, Milligan G. High-affinity interactions between human alpha1A-adrenoceptor C-terminal splice variants produce homo- and heterodimers but do not generate the alpha1L-adrenoceptor. Mol Pharmacol. 2004 Aug;66(2):228-39.

 

Bakker RA, Dees G, Carrillo JJ, Booth RG, López-Gimenez JF, Milligan G, Strange PG, Leurs R. Domain swapping in the human histamine H1 receptor. J Pharmacol Exp Ther. 2004 Oct;311(1):131-8.

 

Milligan G, Lopez-Gimenez J, Wilson S, Carrillo JJ. Selectivity in the oligomerisation of G protein-coupled receptors. Semin Cell Dev Biol. 2004 Jun;15(3):263-8.

 

Gazi L, López-Giménez JF, Rüdiger MP, Strange PG. Constitutive oligomerization of human D2 dopamine receptors expressed in Spodoptera frugiperda 9 (Sf9) and in HEK293 cells. Analysis using co-immunoprecipitation and time-resolved fluorescence resonance energy transfer. Eur J Biochem. 2003 Oct;270(19):3928-38.

 

Gazi L, Wurch T, Lopéz-Giménez JF, Pauwels PJ, Strange PG. Pharmacological analysis of a dopamine D(2Short):G(alphao) fusion protein expressed in Sf9 cells. FEBS Lett. 2003 Jun 19;545(2-3):155-60.

 

Gazi L, López-Giménez JF, Strange PG. Formation of oligomers by G protein-coupled receptors. Curr Opin Drug Discov Devel. 2002 Sep;5(5):756-63.

 

López-Giménez JF, Tecott LH, Palacios JM, Mengod G, Vilaró MT. Serotonin 5- HT (2C) receptor knockout mice: autoradiographic analysis of multiple serotonin receptors. J Neurosci Res. 2002 Jan 1;67(1):69-85.

 

López-Giménez JF, Mengod G, Palacios JM, Vilaró MT. Regional distribution and cellular localization of 5-HT2C receptor mRNA in monkey brain: comparison with [3H]mesulergine binding sites and choline acetyltransferase mRNA. Synapse. 2001 Oct;42(1):12-26.

 

López-Giménez JF, Villazón M, Brea J, Loza MI, Palacios JM, Mengod G, Vilaró MT. Multiple conformations of native and recombinant human 5-hydroxytryptamine(2a) receptors are labeled by agonists and discriminated by antagonists. Mol Pharmacol. 2001 Oct;60(4):690-9.

 

López-Giménez JF, Vilaró MT, Palacios JM, Mengod G. Mapping of 5-HT2A receptors and their mRNA in monkey brain: [3H]MDL100,907 autoradiography and in situ hybridization studies. J Comp Neurol. 2001 Jan 22;429(4):571-89.

 

 

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