Iacovelli, Luisa and Di Menna, Luisa and Peterlik, Daniel and Stangl, Christina and Orlando, Rosamaria and Molinaro, Gemma and De Blasi, Antonio and Bruno, Valeria and Battaglia, Giuseppe and Flor, Peter J. and Uschold-Schmidt, Nicole and Nicoletti, Ferdinando (2017) Type-7 metabotropic glutamate receptors negatively regulate alpha(1)-adrenergic receptor signalling. NEUROPHARMACOLOGY, 113. pp. 343-353. ISSN 0028-3908, 1873-7064
Full text not available from this repository. (Request a copy)Abstract
We studied the interaction between mGlu7 and alpha(1)-adrenergic receptors in heterologous expression systems, brain slices, and living animals. L-2-Amino-4-phosphonobutanoate (L-AP4), and L-serine-O-phosphate (L-SOP), which activate group III mGlu receptors, restrained the stimulation of polyphosphoinositide (PI) hydrolysis induced by the alpha(1)-adrenergic receptor agonist, phenylephrine, in HEK 293 cells co-expressing alpha(1)-adrenergic and mGlu7 receptors. The inibitory action of L-AP4 was abrogated by (i) the mGlu7 receptor antagonist, XAP044; (ii) the C-terminal portion of type-2 G protein coupled receptor kinase; and (iii) the MAP kinase inhibitors, U0126 and PD98059. This suggests that the functional interaction between mGlu7 and alpha(1)-adrenergic receptors was mediated by the beta gamma-subunits of the G(i) protein and required the activation of the MAP kinase pathway. Remarkably, activation of neither mGlu2 nor mGlu4 receptors reduced alpha(1)-adrenergic receptor-mediated PI hydrolysis. In mouse cortical slices, both L-AP4 and L-SOP were able to attenuate norepinephrine- and phenylephrine-stimulated PI hydrolysis at concentrations consistent with the activation of mGlu7 receptors. L-AP4 failed to affect norepinephrine-stimulated PI hydrolysis in cortical slices from mGlu7(-/-) mice, but retained its inhibitory activity in slices from mGlu4(-/-) mice. At behavioural level, i.c.v. injection of phenylephrine produced antidepressant-like effects in the forced swim test. The action of phenylephrine was attenuated by L-SOP, which was inactive per se. Finally, both phenylephrine and L-SOP increased corticosterone levels in mice, but the increase was halved when the two drugs were administered in combination. Our data demonstrate that alpha(1)-adrenergic and mGlu7 receptors functionally interact and suggest that this interaction might be targeted in the treatment of stress-related disorders. (C) 2016 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CEREBROCORTICAL NERVE-TERMINALS; LONG-TERM DEPRESSION; MEDIAL PREFRONTAL CORTEX; MGLU7 RECEPTOR; BETA-ARRESTIN; SYNAPTIC PLASTICITY; MICE LACKING; RAT-BRAIN; PSYCHIATRIC-DISORDERS; ADRENERGIC-RECEPTORS; mGlu7 receptors; alpha(1)-adrenergic receptor; Stress; Cross-talk; G proteins |
| Subjects: | 500 Science > 570 Life sciences 500 Science > 590 Zoological sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Zoologie > Molecular and Cellular Neurobiology (Prof. Dr. Peter J. Flor) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:01 |
| Last Modified: | 19 Feb 2019 09:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/526 |
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