Beta-adrenergic receptor activation increases GABA uptake in adolescent mice frontal cortex: Modulation by cannabinoid receptor agonist WIN55,212-2
| Autor: | Matheus F. Sathler, Alex C. Manhães, Hércules Rezende Freitas, Robertta Silva Martins, Vladimir Pedro Peralva Borges Martins, Luzia da Silva Sampaio, Regina Célia Cussa Kubrusly, Ricardo Augusto de Melo Reis, Maurício dos Santos Pereira, Isis Grigorio de Freitas, Clarissa S. Schitine |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Agonist medicine.medical_specialty GABA Plasma Membrane Transport Proteins Cannabinoid receptor Adrenergic receptor medicine.drug_class medicine.medical_treatment Morpholines Naphthalenes Synaptic Transmission 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Receptor Cannabinoid CB1 Internal medicine Receptors Adrenergic beta medicine Extracellular Cannabinoid receptor type 2 Animals Phenylephrine gamma-Aminobutyric Acid Cannabinoid Receptor Agonists Chemistry Cell Biology Endocannabinoid system Benzoxazines Frontal Lobe 030104 developmental biology Endocrinology nervous system Cannabinoid 030217 neurology & neurosurgery medicine.drug Endocannabinoids Signal Transduction |
| Zdroj: | Neurochemistry international. 120 |
| ISSN: | 1872-9754 |
| Popis: | GABA transporters regulate synaptic GABA levels and dysfunctions in this system might result in psychiatric disorders. The endocannabinoid system (ECS) is the main circuit breaker in the nervous system and may alter noradrenaline (NA) communication, which in turn modulates the release of GABA. However, a close relationship between these systems has not been recognized. We asked whether NA and ECS might control extracellular GABA levels in slices of frontal cortex (FC) of adolescent Swiss mice with 40 days after birth (PN40). Here we show that NA and isoproterenol (ISO), a beta-adrenergic agonist, increased [3H]-GABA uptake in mice FC, while alpha1-adrenergic agonist phenylephrine had no effect. As GAT-1 is expressed and fully functional at the FC, addition of NO-711, a GAT-1 inhibitor, dose dependently blocked [3H]-GABA uptake. The increase of [3H]-GABA uptake induced by ISO was also blocked by NO-711. [3H]-GABA release induced by 80 mM KCl was reduced by NO-711, but not by removal of Ca2+. ISO also increased cyclic AMP (cAMP) levels and addition of WIN 55,212-2, a mixed CB1/CB2 receptor agonist, inhibited the effect of ISO in GABA uptake increase, GAT-1 expression and cAMP levels compared to control. Our data show that GABA transport increased by NA and ISO is negatively regulated by cannabinoid receptor agonist WIN55,212-2. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect