title: The coexistence of multiple receptors in a single nerve terminal provides evidence for pre-synaptic integration.
abstract: Excitatory synaptic transmission is inhibited by G protein coupled receptors, including the adenosine A(1), GABA(B), and metabotropic glutamate receptor 7. These receptors are present in nerve terminals where they reduce the release of glutamate through activating signaling pathways negatively coupled to Ca(2+) channels and adenylyl cyclase. However, it is not clear whether these receptors operate in distinct subpopulations of nerve terminals or if they are co-expressed in the same nerve terminals, despite the functional consequences that such distributions may have on synaptic transmission. Applying Ca(2+) imaging and immunocytochemistry, we show that these three G protein coupled receptors coexist in a subpopulation of cerebrocortical nerve terminals. The three receptors share an intracellular signaling pathway through which their inhibitory responses are integrated and coactivation of these receptors produced an integrated response. Indeed, this response was highly variable, from a synergistic response at subthreshold agonist concentrations to an occluded response at high agonist concentrations. The presence of multiple receptors in a nerve terminal could be responsible for the physiological effects of neurotransmitter spillover from neighboring synapses or alternatively, the co-release of transmitters by the same nerve terminal.
authors.affiliation: Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Ladera
authors.forename: María Del Carmen
authors.initials: Mdel C
authors.lastname: Godino
authors.forename: Ricardo
authors.initials: R
authors.lastname: Martín
authors.forename: Rafael
authors.initials: R
authors.lastname: Luján
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Shigemoto
authors.forename: Francisco
authors.initials: F
authors.lastname: Ciruela
authors.forename: Magdalena
authors.initials: M
authors.lastname: Torres
authors.forename: José
authors.initials: J
authors.lastname: Sánchez-Prieto
mesh_terms: D000241:Adenosine / Q000819:agonists; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000648:ultrastructure; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013347:Subcellular Fractions; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D018755:GABA Agonists; D043682:Receptor, Adenosine A1; D043562:Receptors, G-Protein-Coupled; D018080:Receptors, GABA-B; D018094:Receptors, Metabotropic Glutamate; D017981:Receptors, Neurotransmitter; C102719:metabotropic glutamate receptor 7; D000241:Adenosine; D002118:Calcium