Receptor-receptor interactions: A novel concept in brain integration.
A brief historical presentation of the hypothesis on receptor-receptor interactions as an important integrative mechanism taking place at plasma membrane level is given. Some concepts derived from this integrative mechanism especially the possible assemblage of receptors in receptor mosaics (high-order receptor oligomers) and their relevance for the molecular networks associated with the plasma membrane are discussed. In particular, the Rodbell's disaggregation theory for G-proteins is revisited in the frame of receptor mosaic model. The paper also presents some new indirect evidence on A2A;D2 receptor interactions obtained by means of Atomic Force Microscopy on immunogold preparations of A2A and D2 receptors in CHO cells. These findings support previous data obtained by means of computer-assisted confocal laser microscopy. The allosteric control of G-protein coupled receptors is examined in the light of the new views on allosterism and recent data on a homocysteine analogue capable of modulating D2 receptors are shown. Finally, the hypothesis is introduced on the existence of check-points along the amino acid pathways connecting allosteric and orthosteric binding sites of a receptor and their potential importance for drug development.
Agnati
Luigi F
LF
Department of BioMedical Sciences, University of Modena and IRCCS San Camillo, Lido Venezia, Italy. luigiagnati@tin.it
Guidolin
Diego
D
Leo
Giuseppina
G
Carone
Chiara
C
Genedani
Susanna
S
Fuxe
Kjell
K
D000494:Allosteric Regulation / Q000502:physiology; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000502:physiology* / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D018625:Microscopy, Atomic Force / Q000379:methods; D008954:Models, Biological; D043705:Receptor, Adenosine A2A / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D011954:Receptors, Dopamine / Q000502:physiology
D043705:Receptor, Adenosine A2A; D011956:Receptors, Cell Surface; D011954:Receptors, Dopamine; D006710:Homocysteine