RT Journal Article
SR Electronic
T1 Molecular Mechanisms and Therapeutical Implications of Intramembrane Receptor/Receptor Interactions among Heptahelical Receptors with Examples from the Striatopallidal GABA Neurons
JF Pharmacological Reviews
JO Pharmacol Rev
FD American Society for Pharmacology and Experimental Therapeutics
SP 509
OP 550
DO 10.1124/pr.55.3.2
VO 55
IS 3
A1 Luigi F. Agnati
A1 Sergi Ferré
A1 Carme Lluis
A1 Rafael Franco
A1 Kjell Fuxe
YR 2003
UL http://pharmrev.aspetjournals.org/content/55/3/509.abstract
AB The molecular basis for the known intramembrane receptor/receptor interactions among G protein-coupled receptors was postulated to be heteromerization based on receptor subtype-specific interactions between different types of receptor homomers. The discovery of GABAB heterodimers started this field rapidly followed by the discovery of heteromerization among isoreceptors of several G protein-coupled receptors such as δ/κ opioid receptors. Heteromerization was also discovered among distinct types of G protein-coupled receptors with the initial demonstration of somatostatin SSTR5/dopamine D2 and adenosine A1/dopamine D1 heteromeric receptor complexes. The functional meaning of these heteromeric complexes is to achieve direct or indirect (via adapter proteins) intramembrane receptor/receptor interactions in the complex. G protein-coupled receptors also form heteromeric complexes involving direct interactions with ion channel receptors, the best example being the GABAA/dopamine D5 receptor heteromerization, as well as with receptor tyrosine kinases and with receptor activity modulating proteins. As an example, adenosine, dopamine, and glutamate metabotropic receptor/receptor interactions in the striatopallidal GABA neurons are discussed as well as their relevance for Parkinson's disease, schizophrenia, and drug dependence. The heterodimer is only one type of heteromeric complex, and the evidence is equally compatible with the existence of higher order heteromeric complexes, where also adapter proteins such as homer proteins and scaffolding proteins can exist. These complexes may assist in the process of linking G protein-coupled receptors and ion channel receptors together in a receptor mosaic that may have special integrative value and may constitute the molecular basis for some forms of learning and memory.