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Receptor-receptor interactions, receptor mosaics, and basic principles of molecular network organization

Possible implications for drug development

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Abstract

The phenomenon of receptor-receptor interactions was hypothesized by Agnati and Fuxe in the 1980s, and several indirect proofs were provided in the following years by means of in vitro binding experiments and in vivo experiments in physiological and pathological animal models. This paper aims to outline some of the most important features and consequences of this phenomenon in the frame of the structural and functional aspects of molecular networks. In particular, the concepts of receptor mosaic (RM), and of horizontal and vertical molecular networks (HMNs, VMNs, respectively) are illustrated. To discuss some aspects of the functional organization of molecular networks, not only new data on protein-protein interactions but also the biochemical mechanism of cooperativity will be used. On this basis, some theoretical deductions can be drawn that allow a tentative classification of the RMs and the proposal of the extension of the concept of branching point introduced for enzymes to the possible switching role of some RMs in directing signals to various VMNs. Finally, the cooperativity phenomenon and the so-called symmetry rule will be used to introduce a proper mathematical approach that characterizes RMs as to their receptor composition, receptor topography, and order of receptor activation inside the RM. These new data on G protein-coupled receptors and molecular network organization indicate possible new approaches for drug development.

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Authors and Affiliations

  1. Section of Physiology, Department of Biomedical Sciences, University of Modena, 41100, Modena, Italy

    Luigi F. Agnati

  2. St. Petersburg Institute for Informatics and Automation, Russian Academy of Sciences, St. Petersburg, Russia

    Alexander O. Tarakanov

  3. Behavioral Neuroscience Branch, National Institute on Drug Abuse, NIH, DHHS, 20817, Baltimore, MD

    Sergi Ferré

  4. Department of Neuroscience, Division of Cellular and Molecular Neurochemistry, Karolinska Institute, S-171 77, Stockholm, Sweden

    Kjell Fuxe

  5. Department of Anatomy and Physiology, University of Padua, Padua, Italy

    Diego Guidolin

Authors
  1. Luigi F. Agnati
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  2. Alexander O. Tarakanov
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  3. Sergi Ferré
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  4. Kjell Fuxe
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  5. Diego Guidolin
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Corresponding author

Correspondence to Luigi F. Agnati.

Additional information

This paper is dedicated to Professor Ermanno Manni, former Professor of Human Physiology in Rome.

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Agnati, L.F., Tarakanov, A.O., Ferré, S. et al. Receptor-receptor interactions, receptor mosaics, and basic principles of molecular network organization. J Mol Neurosci 26, 193–208 (2005). https://doi.org/10.1385/JMN:26:2-3:193

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