title: Cross-talk between metabotropic glutamate receptor 7 and beta adrenergic receptor signaling at cerebrocortical nerve terminals.
abstract: The co-existence of presynaptic G protein coupled receptors, GPCRs, has received little attention, despite the fact that interplay between the signaling pathways activated by such receptors may affect the neurotransmitter release. Using immunocytochemistry and immuhistochemistry we show that mGlu7 and β-adrenergic receptors are co-expressed in a sub-population of cerebrocortical nerve terminals. mGlu7 receptors readily couple to pathways that inhibit glutamate release. We found that when mGlu7 receptors are also coupled to pathways that enhance glutamate release by prolonged exposure to agonist, and β-adrenergic receptors are also activated, a cross-talk between their signaling pathways occurs that affect the overall release response. This interaction is the result of mGlu7 receptors inhibiting the adenylyl cyclase activated by β adrenergic receptors. Thus, blocking Gi/o proteins with pertussis toxin provokes a further increase in release after receptor co-activation which is also observed after activating β-adrenergic receptor signaling pathways downstream of adenylyl cyclase with the cAMP analog Sp8Br or 8pCPT-2-OMe-cAMP (a specific activator of the guanine nucleotide exchange protein directly activated by cAMP, EPAC). Co-activation of mGlu7 and β-adrenergic receptors also enhances PLC-dependent accumulation of IP1 and the translocation of the active zone protein Munc13-1 to the membrane, indicating that release potentiation by these receptors involves the modulation of the release machinery.
authors.affiliation: Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, 28040 Madrid, Spain; Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Hospital Clínico San Carlos, C/Profesor Martín Lagos s/n, Madrid 28040, Spain.
authors.forename: José Javier
authors.initials: JJ
authors.lastname: Ferrero
authors.affiliation: Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, 28040 Madrid, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Ramírez-Franco
authors.affiliation: Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, 28040 Madrid, Spain; Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Hospital Clínico San Carlos, C/Profesor Martín Lagos s/n, Madrid 28040, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Martín
authors.affiliation: Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, 28040 Madrid, Spain; Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Hospital Clínico San Carlos, C/Profesor Martín Lagos s/n, Madrid 28040, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Bartolomé-Martín
authors.affiliation: Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, 28040 Madrid, Spain; Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Hospital Clínico San Carlos, C/Profesor Martín Lagos s/n, Madrid 28040, Spain.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Torres
authors.affiliation: Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, 28040 Madrid, Spain; Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Hospital Clínico San Carlos, C/Profesor Martín Lagos s/n, Madrid 28040, Spain. Electronic address: jsprieto@vet.ucm.es.
authors.forename: José
authors.initials: J
authors.lastname: Sánchez-Prieto
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D061207:Calcium Ionophores / Q000494:pharmacology; D002531:Cerebellum / Q000166:cytology; D002540:Cerebral Cortex / Q000166:cytology; D000242:Cyclic AMP / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007295:Inositol Phosphates / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: C114785:2-amino-4-phosphono-propinate; C105593:8-bromoadenosine-3',5'-cyclic monophosphorothioate; D061207:Calcium Ionophores; D007295:Inositol Phosphates; D009419:Nerve Tissue Proteins; D011422:Propionates; D011943:Receptors, Adrenergic, beta; D018094:Receptors, Metabotropic Glutamate; D016708:Synaptophysin; D013873:Thionucleotides; C503321:Unc13a protein, mouse; C102719:metabotropic glutamate receptor 7; D015124:8-Bromo Cyclic Adenosine Monophosphate; D018698:Glutamic Acid; D015759:Ionomycin; D000242:Cyclic AMP
keywords: G protein coupled receptors (GPCRs); Glutamate release; Metabotropic glutamate receptor 7 (mGlu7 receptor); cAMP; β-adrenergic receptors