| Annotated protein: | Alpha-2A adrenergic receptor (Alpha-2A adrenoreceptor) (Alpha-2A adrenoceptor) (Alpha-2AAR). Gene symbol: ADRA2A. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q01338 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ ADRA2A |
| Ontology domain: | Biological Process |
| SynGO term: | presynaptic modulation of chemical synaptic transmission (GO:0099171) |
| Synapse type(s): | cerebral cortex, dopaminergic basal ganglia, dopaminergic |
| Annotated paper: | Bucheler MM, et al. "Two alpha(2)-adrenergic receptor subtypes, alpha(2A) and alpha(2C), inhibit transmitter release in the brain of gene-targeted mice" Neuroscience. 2002;109(4):819-26 PMID:11927164 |
| Figure(s): | Fig.1-4 |
| Annotation description: | This paper systematically analyzed the functional consequences of loss of individual and multiple G-Protein coupled alpha2A adrenergic receptor (AR) subtypes using alpha2A-, alpha2B-, and alpha2C-KO mice. Receptor autoradiography using radiolabelled RX821002 revealed that alpha2A-and -2C are the two main alpha2 subtypes expressed in the mouse brain. Only the alpha2AC-DKO shows a complete loss of receptor labelling (Fig. 1A). These findings were confirmed by using a radioligand binding assay in purified brain synaptosomes (Fig. 1B). In wildtype acute slices of mouse cortex, application of the alpha2-agonist UK14,304 (Fig. 2A, B) or norepinephrine (Fig. 2C) caused an inhibition of radiolabelled norepinephrine release. In slices from alpha2A-KO and -2AC-DKO mice, norepinephrine release is not inhibited (Fig. 2B, C). Extensive electrical stimulation induces endogenous norepinephrine release caused an inhibition of radiolabelled norepinephrine in control slices, but not in -2AC-DKO slices, indicating that alpha2-ARs are presynaptic autoreceptors that inhibit synaptic transmission upon activation. Further, exogenous application of the alpha2-agonist UK14,304 causes a reduction in radiolabelled dopamine release from basal ganglia from wildtype mice that is only little affected in alpha2AC-DKO mice (Fig. 4B). Also presynaptic glutamate release have been shown to be affected upon activation of presynaptic alpha2-ARs probably due to inhibition of presynaptic N-type Ca2+-channels and activation of inwardly-rectifying K+-channels (see linked papers). |
| Evidence tracking, Biological System: | Intact tissue |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) Antagonist / agonist |
| Evidence tracking, Experiment Assay: | radioisotope assay evidence |
| Annotator(s): | Noa Lipstein (ORCID:0000-0002-0755-5899) Cordelia Imig (ORCID:0000-0001-7351-8706) Vincent O'connor (ORCID:0000-0003-3185-5709) Nils Brose (ORCID:0000-0003-0938-8534) |
| Lab: | Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany |
| Additional literature: | Activation of presynaptic G-protein coupled Alpha2 adrenergic receptors (ARs) causes a decrease in excitatory neurotransmission in the ventral tegmental area. Application of the alpha2-AR agonist clonidine induces a reduction in the spontaneous (s)EPSC (Fig. 5) and mini (m)EPSC frequency (Fig.6), without a change in the mEPSC amplitude. These findings indicate that the activation of presynaptic alpha2-ARs modulates synaptic transmission. @ PMID:22564071 The data presented in this paper indicates that the reduction in presynaptic neurotransmission upon activation of alpha2-AR activation is due to inhibition of presynaptic N-type Ca2+-channels and activation of inwardly-rectifying K+-channels. @ PMID:12713644 |
| SynGO annotation ID: | 1100 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |