The inhibition of release by mGlu7 receptors is independent of the Ca2+ channel type but associated to GABAB and adenosine A1 receptors.
Neurotransmitter release is inhibited by G-protein coupled receptors (GPCRs) through signalling pathways that are negatively coupled to Ca2+ channels and adenylyl cyclase. Through Ca2+ imaging and immunocytochemistry, we have recently shown that adenosine A1, GABAB and the metabotropic glutamate type 7 receptors coexist in a subset of cerebrocortical nerve terminals. As these receptors inhibit glutamate release through common intracellular signalling pathways, their co-activation occluded each other responses. Here we have addressed whether the occlusion of receptor responses is restricted to the glutamate release mediated by N-type Ca2+ channels by analysing this process in nerve terminals from mice lacking the alpha1B subunit (Cav 2.2) of these channels. We found that glutamate release from cerebrocortical nerve terminals without these channels, in which release relies exclusively on P/Q type Ca2+ channels, is not modulated by mGlu7 receptors. Furthermore, there is no occlusion of the release inhibition by GABAB and adenosine A1. Hence, in the cerebrocortical preparation, these three receptors only appear to coexist in N-type channel containing nerve terminals. In contrast, in hippocampal nerve terminals lacking this subunit, where mGlu7 receptors modulate glutamate release via P/Q type channels, the occlusion of inhibitory responses by co-stimulation of adenosine A1, GABAB and mGlu7 receptors was observed. Thus, occlusion of the responses by the three GPCRs is independent of the Ca2+ channel type but rather, it is associated to functional mGlu7 receptors.
Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense de Madrid, Avda Puerta de Hierro s/n, 28040 Madrid, Spain.
Ricardo
R
Martín
Carolina
C
Ladera
David
D
Bartolomé-Martín
Magdalena
M
Torres
José
J
Sánchez-Prieto
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000172:deficiency / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D011422:Propionates / Q000494:pharmacology; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
C114785:2-amino-4-phosphono-propinate; C500963:Cacna1b protein, mouse; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D011422:Propionates; D043682:Receptor, Adenosine A1; D018080:Receptors, GABA-B; D018094:Receptors, Metabotropic Glutamate; C102719:metabotropic glutamate receptor 7; D020867:omega-Agatoxin IVA; D018698:Glutamic Acid; D020866:omega-Conotoxin GVIA; D001418:Baclofen; D002118:Calcium