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Review Article

The changing world of G protein-coupled receptors: from monomers to dimers and receptor mosaics with allosteric receptor–receptor interactions

, , , , , , & show all
Pages 272-283 | Received 15 Jun 2010, Accepted 01 Jul 2010, Published online: 04 Aug 2010

References

  • Dixon RA, Kobilka BK, Strader DJ, Benovic JL, Dohlman HG, Frielle T, Bolanowski MA, Bennett CD, Rands E, Diehl RE, Mumford RA, Slater EE, Sigal IS, Caron MG, Lefkowitz RJ, Strader CD. Cloning of the gene and cDNA for mammalian beta-adrenergic receptor and homology with rhodopsin. Nature 1986, 321, 75–79.
  • Lefkowitz RJ. The superfamily of heptahelical receptors. Nat Cell Biol 2000, 2, E133–E136.
  • Rasmussen SG, Choi HJ, Rosenbaum DM, Kobilka TS, Thian FS, Edwards PC, Burghammer M, Ratnala VR, Sanishvili R, Fischetti RF, Schertler GF, Weis WI, Kobilka BK. Crystal structure of the human beta2 adrenergic G protein-coupled receptor. Nature 2007, 450, 383–387.
  • Rosenbaum DM, Rasmussen SG, Kobilka BK. The structure and function of G protein-coupled receptors. Nature 2009, 459, 356–363.
  • Schwartz TW, Frimurer TM, Holst B, Rosenkilde MM, Elling CE. Molecular mechanism of 7TM receptor activation–a global toggle switch model. Annu Rev Pharmacol Toxicol 2006, 46, 481–519.
  • Nygaard R, Frimurer TM, Holst B, Rosenkilde MM, Schwartz TW. Ligand binding and micro-switches in 7TM receptor structures. Trends Pharmacol Sci 2009, 30, 249–259.
  • Dahlstroem A, Fuxe K. Evidence for the existence of monoamine-containing neurons in the central nervous system. i. demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol Scand Suppl 1964, (Suppl 232), 1–55.
  • Fuxe K. Evidence for the existence of monoamine neurons in the central nervous system. IV. Distribution of monoamine nerve terminals in the central nervous system. Acta Physiol Scand 1965, 64 (Suppl 247), 39–85.
  • Fuxe K, Dahlström A. Evidence for the Existence of Central Monoamine Neurons: Mapping of Central Dopamine, Noradrenaline and 5-Hydroxytryptamine Neurons in the Central Nervous System with Transmitter Histochemistry. Saarbrucken: VDM Verlag Dr. Muller Aktiengesellschaft & Co. KG, 2009.
  • Hökfelt T, Fuxe K, Pernow B. Coexistence of Neuronal Messengers: a New Principle in Chemical Transmission. Amsterdam, New York, Oxford: Elsevier, 1986.
  • Eccles JC, Fatt P, Koketsu K. Cholinergic and inhibitory synapses in a pathway from motor-axon collaterals to motoneurones. J Physiol (Lond) 1954, 126, 524–562.
  • Kandel ER. Cellular Basis of Behaviour. An introduction to behavioural neurobiology. San Francisco: W.H. Freeman and Company, 1976.
  • Fuxe K, Dahlström A, Höistad M, Marcellino D, Jansson A, Rivera A, Diaz-Cabiale Z, Jacobsen K, Tinner-Staines B, Hagman B, Leo G, Staines W, Guidolin D, Kehr J, Genedani S, Belluardo N, Agnati LF. From the Golgi-Cajal mapping to the transmitter-based characterization of the neuronal networks leading to two modes of brain communication: wiring and volume transmission. Brain Res Rev 2007, 55, 17–54.
  • Fuxe K, Dahlström AB, Jonsson G, Marcellino D, Guescini M, Dam M, Manger P, Agnati L. The discovery of central monoamine neurons gave volume transmission to the wired brain. Prog Neurobiol 2010, 90, 82–100.
  • Agnati LF, Guidolin D, Guescini M, Genedani S, Fuxe K. Understanding wiring and volume transmission. Brain Res Rev 2010, 64, 137–159.
  • Agnati LF, Fuxe K, Zini I, Lenzi P, Hökfelt T. Aspects on receptor regulation and isoreceptor identification. Med Biol 1980, 58, 182–187.
  • Agnati LF, Fuxe K, Zoli M, Rondanini C, Ogren SO. New vistas on synaptic plasticity: the receptor mosaic hypothesis of the engram. Med Biol 1982, 60, 183–190.
  • Fuxe K, Agnati LF, Benfenati F, Cimmino M, Algeri S, Hökfelt T, Mutt V. Modulation by cholecystokinins of 3H-spiroperidol binding in rat striatum: evidence for increased affinity and reduction in the number of binding sites. Acta Physiol Scand 1981, 113, 567–569.
  • Fuxe K, Agnati LF, Benfenati F, Celani M, Zini I, Zoli M, Mutt V. Evidence for the existence of receptor–receptor interactions in the central nervous system. Studies on the regulation of monoamine receptors by neuropeptides. J Neural Transm Suppl 1983, 18, 165–179.
  • Limbird LE, Meyts PD, Lefkowitz RJ. Beta-adrenergic receptors: evidence for negative co-operativity. Biochem Biophys Res Commun 1975, 64, 1160–1168.
  • Fuxe K, Agnati LF, Härfstrand A, Janson AM, Neumeyer A, Andersson K, Ruggeri M, Zoli M, Goldstein M. Morphofunctional studies on the neuropeptide Y/adrenaline costoring terminal systems in the dorsal cardiovascular region of the medulla oblongata. Focus on receptor–receptor interactions in cotransmission. Prog Brain Res 1986, 68, 303–320.
  • Fuxe K, Härfstrand A, Agnati LF, Kalia M, Fredholm B, Svensson T, Gustafsson JA, Lang R, Ganten D. Central catecholamine-neuropeptide Y interactions at the pre- and postsynaptic level in cardiovascular centers. J Cardiovasc Pharmacol 1987, 10(Suppl 12), S1–S13.
  • Härfstrand A, Fuxe K. Simultaneous central administration of adrenaline and neuropeptide Y leads to antagonistic interactions in vasodepressor responses in awake male rats. Acta Physiol Scand 1987, 130, 529–531.
  • Härfstrand A, Fuxe K, Agnati L, Fredholm B. Reciprocal interactions between alpha 2-adrenoceptor agonist and neuropeptide Y binding sites in the nucleus tractus solitarius of the rat. A biochemic and autoradiographic analysis. J Neural Transm 1989, 75, 83–99.
  • Yang SN, Fior DR, Hedlund PB, Agnati LF, Fuxe K. Antagonistic regulation of alpha 2-adrenoceptors by neuropeptide Y receptor subtypes in the nucleus tractus solitarii. Eur J Pharmacol 1994, 271, 201–212.
  • Agnati LF, Fuxe K, Zoli M, Pich EM, Benfenati F, Zini I, Goldstein M. Aspects on the information handling by the central nervous system: focus on cotransmission in the aged rat brain. Prog Brain Res 1986, 68, 291–301.
  • Vilardaga JP, Agnati LF, Fuxe K, Ciruela F. GPCR heteromer dynamics at a glance. J Cell Sci 2010 (In Press).
  • Hofmann KP, Scheerer P, Hildebrand PW, Choe HW, Park JH, Heck M, Ernst OP. A G protein-coupled receptor at work: the rhodopsin model. Trends Biochem Sci 2009, 34, 540–552.
  • Lohse MJ, Benovic JL, Codina J, Caron MG, Lefkowitz RJ. beta-Arrestin: a protein that regulates beta-adrenergic receptor function. Science 1990, 248, 1547–1550.
  • Ferguson SS, Downey WE 3rd, Colapietro AM, Barak LS, Ménard L, Caron MG. Role of beta-arrestin in mediating agonist-promoted G protein-coupled receptor internalization. Science 1996, 271, 363–366.
  • Lefkowitz RJ. G protein-coupled receptors. III. New roles for receptor kinases and beta-arrestins in receptor signaling and desensitization. J Biol Chem 1998, 273, 18677–18680.
  • Lefkowitz RJ, Shenoy SK. Transduction of receptor signals by beta-arrestins. Science 2005, 308, 512–517.
  • Beaulieu JM, Gainetdinov RR, Caron MG. Akt/GSK-3 signaling in the action of psychotropic drugs. Annu Rev Pharmacol Toxicol 2009, 49, 327–347.
  • Vilardaga JP, Bünemann M, Krasel C, Castro M, Lohse MJ. Measurement of the millisecond activation switch of G protein-coupled receptors in living cells. Nat Biotechnol 2003, 21, 807–812.
  • Vilardaga JP, Bünemann M, Feinstein TN, Lambert N, Nikolaev VO, Engelhardt S, Lohse MJ, Hoffmann C. GPCR and G proteins: drug efficacy and activation in live cells. Mol Endocrinol 2009, 23, 590–599.
  • Castro M, Nikolaev VO, Palm D, Lohse MJ, Vilardaga JP. Turn-on switch in parathyroid hormone receptor by a two-step parathyroid hormone binding mechanism. Proc Natl Acad Sci USA 2005, 102, 16084–16089.
  • Hein P, Rochais F, Hoffmann C, Dorsch S, Nikolaev VO, Engelhardt S, Berlot CH, Lohse MJ, Bünemann M. Gs activation is time-limiting in initiating receptor-mediated signaling. J Biol Chem 2006, 281, 33345–33351.
  • Ferrandon S, Feinstein TN, Castro M, Wang B, Bouley R, Potts JT, Gardella TJ, Vilardaga JP. Sustained cyclic AMP production by parathyroid hormone receptor endocytosis. Nat Chem Biol 2009, 5, 734–742.
  • Agnati LF, Guidolin D, Leo G, Fuxe K. A boolean network modeling of receptor mosaics relevance of topology and co-operativity. J Neural Transm 2007, 114, 77–92.
  • Fuxe K, Canals M, Torvinen M, Marcellino D, Terasmaa A, Genedani S, Leo G, Guidolin D, Diaz-Cabiale Z, Rivera A, Lundstrom L, Langel U, Narvaez J, Tanganelli S, Lluis C, Ferré S, Woods A, Franco R, Agnati LF. Intramembrane receptor–receptor interactions: a novel principle in molecular medicine. J Neural Transm 2007, 114, 49–75.
  • Zoli M, Agnati LF, Hedlund PB, Li XM, Ferré S, Fuxe K. Receptor–receptor interactions as an integrative mechanism in nerve cells. Mol Neurobiol 1993, 7, 293–334.
  • Magalhaes AC, Holmes KD, Dale LB, Comps-Agrar L, Lee D, Yadav PN, Drysdale L, Poulter MO, Roth BL, Pin JP, Anisman H, Ferguson SS. CRF receptor 1 regulates anxiety behavior via sensitization of 5-HT2 receptor signaling. Nat Neurosci 2010, 13, 622–629.
  • Marshall FH, Jones KA, Kaupmann K, Bettler B. GABAB receptors—the first 7TM heterodimers. Trends Pharmacol Sci 1999, 20, 396–399.
  • Marshall FH. Is the GABA B heterodimer a good drug target? J Mol Neurosci 2005, 26, 169–176.
  • Gurevich VV, Gurevich EV. How and why do GPCRs dimerize? Trends Pharmacol Sci 2008, 29, 234–240.
  • Gurevich VV, Gurevich EV. GPCR monomers and oligomers: it takes all kinds. Trends Neurosci 2008, 31, 74–81.
  • Fuxe K, Agnati LF. Receptor–receptor Interaction. A New Intramembrane Integrative Mechanism. London: MacMillan Press, 1987.
  • Kenakin T, Agnati LF, Caron MG, Fredholm B, Guidolin D, Kobilka BK, Lefkowitz R, Lohse M, Woods A, Fuxe K. Summary of workshop on G Protein-coupled receptors. J Recept Signal Transduct 2010 (In Press).
  • Bridgman P. Operational Analysis. J Philos Sci 1938, 5, 114–131.
  • Ferré S, Baler R, Bouvier M, Caron MG, Devi LA, Durroux T, Fuxe K, George SR, Javitch JA, Lohse MJ, Mackie K, Milligan G, Pfleger KD, Pin JP, Volkow ND, Waldhoer M, Woods AS, Franco R. Building a new conceptual framework for receptor heteromers. Nat Chem Biol 2009, 5, 131–134.
  • Guo W, Urizar E, Kralikova M, Mobarec JC, Shi L, Filizola M, Javitch JA. Dopamine D2 receptors form higher-order oligomers at physiological expression levels. EMBO J 2008, 27, 2293–2304.
  • Carriba P, Navarro G, Ciruela F, Ferré S, Casadó V, Agnati L, Cortés A, Mallol J, Fuxe K, Canela EI, Lluís C, Franco R. Detection of heteromerization of more than two proteins by sequential BRET-FRET. Nat Methods 2008, 5, 727–733.
  • Cabello N, Gandía J, Bertarelli DC, Watanabe M, Lluís C, Franco R, Ferré S, Luján R, Ciruela F. Metabotropic glutamate type 5, dopamine D2 and adenosine A2a receptors form higher-order oligomers in living cells. J Neurochem 2009, 109, 1497–1507.
  • Agnati LF, Guidolin D, Vilardaga JP, Ciruela F, Fuxe K. On the expanding terminology in the GPCR field: The meaning of receptor mosaics and receptor heteromers. J Recept Signal Transduct Res 2010 (In Press).
  • Agnati LF, Guidolin D, Albertin G, Trivello E, Ciruela F, Genedani S, Tarakanov A, Fuxe K. An integrated view on the role of receptor mosaics at perisynaptic level: focus on adenosine A(2A), dopamine D(2), cannabinoid CB(1), and metabotropic glutamate mGlu(5) receptors. J Recept Signal Transduct Res 2010 (In Press).
  • Fuxe K, Marcellino D, Guidolin D, Woods AS, Agnati LF. Heterodimers and receptor mosaics of different types of G protein-coupled receptors. Physiology (Bethesda) 2008, 23, 322–332.
  • Fuxe K, Marcellino D, Rivera A, Diaz-Cabiale Z, Filip M, Gago B, Roberts DC, Langel U, Genedani S, Ferraro L, de la Calle A, Narvaez J, Tanganelli S, Woods A, Agnati LF. Receptor-receptor interactions within receptor mosaics. Impact on neuropsychopharmacology. Brain Res Rev 2008, 58, 415–452.
  • Fuxe K, Marcellino D, Borroto-Escuela DO, Guescini M, Fernandez-Duenas V, Tanganelli S, Rivera A, Ciruela F, Agnati LF. Adenosine-dopamine interactions in the pathophysiology and treatment of CNS disorders. CNS Neurosci Ther 2010, 16, e1–e18.
  • Fuxe K, Marcellino D, Leo G, Agnati LF. Molecular integration via allosteric interactions in receptor heteromers. A working hypothesis. Curr Opin Pharmacol 2010, 10, 14–22.
  • Agnati LF, Guidolin D, Leo G, Carone C, Genedani S, Fuxe K. Receptor–receptor interactions: A novel concept in brain integration. Prog Neurobiol 2010, 90, 157–175.
  • Agnati LF, Franzen O, Ferré S, Leo G, Franco R, Fuxe K. Possible role of intramembrane receptor–receptor interactions in memory and learning via formation of long-lived heteromeric complexes: focus on motor learning in the basal ganglia. J Neural Transm Suppl 2003, 1–28.
  • Fuxe K, Marcellino D, Woods AS, Giuseppina L, Antonelli T, Ferraro L, Tanganelli S, Agnati LF. Integrated signaling in heterodimers and receptor mosaics of different types of GPCRs of the forebrain: relevance for schizophrenia. J Neural Transm 2009, 116, 923–939.
  • Rozenfeld R, Devi LA. Receptor heteromerization and drug discovery. Trends Pharmacol Sci 2010, 31, 124–130.
  • Kenakin TP. ‘7TM receptor allostery: putting numbers to shapeshifting proteins. Trends Pharmacol Sci 2009, 30, 460–469.
  • Kenakin TP. Seven transmembrane receptors as nature’s prototype allosteric protein: de-emphasizing the geography of binding. Mol Pharmacol 2008, 74, 541–543.
  • Kenakin T. New concepts in drug discovery: collateral efficacy and permissive antagonism. Nat Rev Drug Discov 2005, 4, 919–927.
  • Monod J, Wyman J, Changeux JP. On the nature of allosteric transitions: a plausible model. J Mol Biol 1965, 12, 88–118.
  • Koshland DE Jr, Némethy G, Filmer D. Comparison of experimental binding data and theoretical models in proteins containing subunits. Biochemistry 1966, 5, 365–385.
  • Tsai CJ, Del Sol A, Nussinov R. Protein allostery, signal transmission and dynamics: a classification scheme of allosteric mechanisms. Mol Biosyst 2009, 5, 207–216.
  • Ciruela F, Burgueño J, Casadó V, Canals M, Marcellino D, Goldberg SR, Bader M, Fuxe K, Agnati LF, Lluis C, Franco R, Ferré S, Woods AS. Combining mass spectrometry and pull-down techniques for the study of receptor heteromerization. Direct epitope-epitope electrostatic interactions between adenosine A2A and dopamine D2 receptors. Anal Chem 2004, 76, 5354–5363.
  • Fuxe K, Ferré S, Canals M, Torvinen M, Terasmaa A, Marcellino D, Goldberg SR, Staines W, Jacobsen KX, Lluis C, Woods AS, Agnati LF, Franco R. Adenosine A2A and dopamine D2 heteromeric receptor complexes and their function. J Mol Neurosci 2005, 26, 209–220.
  • Woods AS, Ciruela F, Fuxe K, Agnati LF, Lluis C, Franco R, Ferré S. Role of electrostatic interaction in receptor–receptor heteromerization. J Mol Neurosci 2005, 26, 125–132.
  • Torvinen M, Marcellino D, Canals M, Agnati LF, Lluis C, Franco R, Fuxe K. Adenosine A2A receptor and dopamine D3 receptor interactions: evidence of functional A2A/D3 heteromeric complexes. Mol Pharmacol 2005, 67, 400–407.
  • Woods AS. The mighty arginine, the stable quaternary amines, the powerful aromatics, and the aggressive phosphate: their role in the noncovalent minuet. J Proteome Res 2004, 3, 478–484.
  • Borroto-Escuela DO, Marcellino D, Narvaez M, Flajolet M, Heintz N, Agnati L, Ciruela F, Fuxe K. A serine point mutation in the adenosine A2AR C-terminal tail reduces receptor heteromerization and allosteric modulation of the dopamine D2R. Biochem Biophys Res Commun 2010, 394, 222–227.
  • Vilardaga JP, Nikolaev VO, Lorenz K, Ferrandon S, Zhuang Z, Lohse MJ. Conformational cross-talk between alpha2A-adrenergic and mu-opioid receptors controls cell signaling. Nat Chem Biol 2008, 4, 126–131.
  • Fuxe K, Agnati LF, Härfstrand A, Fredholm BB, Kalia M, Goldstein M. On the role of receptor-recceptor interaction in synaptic transmission: biochemical and autoradiographical studies on the interacions between alpha2-adrenergic and neuropeptide Y receptors in the nucleus tranctus solitarius. In: Fuxe K, Agnati LF, eds. Receptor–Receptor Interactions. A New Intramembrane Integrative Mechanism. London: MacMillan Press, 1987, 222–235.
  • Han Y, Moreira IS, Urizar E, Weinstein H, Javitch JA. Allosteric communication between protomers of dopamine Class A GPCR dimers modulates activation. Nat Chem Biol 2009, 5, 688–695.
  • Schwartz TW, Holst B. Ago-allosteric modulation and other types of allostery in dimeric 7TM receptors. J Recept Signal Transduct Res 2006, 26, 107–128.
  • Schwartz TW, Holst B. Allosteric enhancers, allosteric agonists and ago-allosteric modulators: where do they bind and how do they act? Trends Pharmacol Sci 2007, 28, 366–373.
  • 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, 26, 2080–2087.
  • Marcellino D, Ferré S, Casadó V, Cortés A, Le Foll B, Mazzola C, Drago F, Saur O, Stark H, Soriano A, Barnes C, Goldberg SR, Lluis C, Fuxe K, Franco R. Identification of dopamine D1-D3 receptor heteromers. Indications for a role of synergistic D1-D3 receptor interactions in the striatum. J Biol Chem 2008, 283, 26016–26025.
  • Fiorentini C, Busi C, Gorruso E, Gotti C, Spano P, Missale C. Reciprocal regulation of dopamine D1 and D3 receptor function and trafficking by heterodimerization. Mol Pharmacol 2008, 74, 59–69.
  • Hillion J, Canals M, Torvinen M, Casado V, Scott R, Terasmaa A, Hansson A, Watson S, Olah ME, Mallol J, Canela EI, Zoli M, Agnati LF, Ibanez CF, Lluis C, Franco R, Ferre S, Fuxe K. Coaggregation, cointernalization, and codesensitization of adenosine A2A receptors and dopamine D2 receptors. J Biol Chem 2002, 277, 18091–18097.
  • Fuxe K, Ferré S, Zoli M, Agnati LF. Integrated events in central dopamine transmission as analyzed at multiple levels. Evidence for intramembrane adenosine A2A/dopamine D2 and adenosine A1/dopamine D1 receptor interactions in the basal ganglia. Brain Res Brain Res Rev 1998, 26, 258–273.
  • Azdad K, Gall D, Woods AS, Ledent C, Ferré S, Schiffmann SN. Dopamine D2 and adenosine A2A receptors regulate NMDA-mediated excitation in accumbens neurons through A2A-D2 receptor heteromerization. Neuropsychopharmacology 2009, 34, 972–986.
  • Agnati LF, Ferré S, Lluis C, Franco R, Fuxe K. Molecular mechanisms and therapeutical implications of intramembrane receptor/receptor interactions among heptahelical receptors with examples from the striatopallidal GABA neurons. Pharmacol Rev 2003, 55, 509–550.
  • Woods AS, Marcellino D, Jackson SN, Franco R, Ferré S, Agnati LF, Fuxe K. How calmodulin interacts with the adenosine A(2A) and the dopamine D(2) receptors. J Proteome Res 2008, 7, 3428–3434.
  • Navarro G, Aymerich MS, Marcellino D, Cortés A, Casadó V, Mallol J, Canela EI, Agnati L, Woods AS, Fuxe K, Lluís C, Lanciego JL, Ferré S, Franco R. Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors. J Biol Chem 2009, 284, 28058–28068.
  • Ferré S, Woods AS, Navarro G, Aymerich M, Lluís C, Franco R. Calcium-mediated modulation of the quaternary structure and function of adenosine A2A-dopamine D2 receptor heteromers. Curr Opin Pharmacol 2010, 10, 67–72.
  • Lingwood D, Simons K. Lipid rafts as a membrane-organizing principle. Science 2010, 327, 46–50.
  • Fantini J. How sphingolipids bind and shape proteins: molecular basis of lipid-protein interactions in lipid shells, rafts and related biomembrane domains. Cell Mol Life Sci 2003, 60, 1027–1032.
  • Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Kuhn P, Weis WI, Kobilka BK, Stevens RC. High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science 2007, 318, 1258–1265.
  • Barki-Harrington L, Luttrell LM, Rockman HA. Dual inhibition of beta-adrenergic and angiotensin II receptors by a single antagonist: a functional role for receptor–receptor interaction in vivo. Circulation 2003, 108, 1611–1618.
  • Mercier JF, Salahpour A, Angers S, Breit A, Bouvier M. Quantitative assessment of beta 1- and beta 2-adrenergic receptor homo- and heterodimerization by bioluminescence resonance energy transfer. J Biol Chem 2002, 277, 44925–44931.
  • Lavoie C, Mercier JF, Salahpour A, Umapathy D, Breit A, Villeneuve LR, Zhu WZ, Xiao RP, Lakatta EG, Bouvier M, Hébert TE. Beta 1/beta 2-adrenergic receptor heterodimerization regulates beta 2-adrenergic receptor internalization and ERK signaling efficacy. J Biol Chem 2002, 277, 35402–35410.
  • Breit A, Lagacé M, Bouvier M. Hetero-oligomerization between beta2- and beta3-adrenergic receptors generates a beta-adrenergic signaling unit with distinct functional properties. J Biol Chem 2004, 279, 28756–28765.
  • AbdAlla S, Lother H, Quitterer U. AT1-receptor heterodimers show enhanced G protein activation and altered receptor sequestration. Nature 2000, 407, 94–98.
  • AbdAlla S, Lother H, el Massiery A, Quitterer U. Increased AT(1) receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsiveness. Nat Med 2001, 7, 1003–1009.
  • AbdAlla S, Abdel-Baset A, Lother H, el Massiery A, Quitterer U. Mesangial AT1/B2 receptor heterodimers contribute to angiotensin II hyper-responsiveness in experimental hypertension. J Mol Neurosci 2005, 26, 185–192.
  • Fior DR, Hedlund PB, Fuxe K. Autoradiographic evidence for a bradykinin/angiotensin II receptor–receptor interaction in the rat brain. Neurosci Lett 1993, 163, 58–62.

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