loading page

Transporters involved in adult rat cortical astrocyte dopamine uptake: kinetics, expression and pharmacological modulation
  • Vesna Socan,
  • Mojca Kržan,
  • Klemen Dolinar
Vesna Socan
University of Ljubljana Faculty of Medicine

Corresponding Author:vesna.socan@mf.uni-lj.si

Author Profile
Mojca Kržan
University of Ljubljana Faculty of Medicine
Author Profile
Klemen Dolinar
University of Ljubljana Faculty of Medicine
Author Profile

Abstract

Astrocytes, glial cells in the central nervous system, perform a multitude of homeostatic functions and are in constant bidirectional communication with neuronal cells, a concept named the tripartite synapse, however their role in the dopamine homeostasis remains unexplored. The aim of this study was to clarify the pharmacological and molecular characteristics of dopamine transport in cultured cortical astrocytes of adult rats. In addition, we were interested in the expression of mRNA of dopamine transporters as well as dopamine receptors D1 and D2 and in the effect of dopaminergic drugs on the expression of these transporters and receptors. We have found that astrocytes possess both Na+-dependent and Na+-independent transporters. Uptake of radiolabelled dopamine was time-, temperature- and concentration-dependent and was inhibited by decynium-22, a plasma membrane monoamine transporter inhibitor, tricyclic antidepressants desipramine and nortriptyline, both inhibitors of the norepinephrine transporter. Results of transporter mRNA expression indicate that the main transporters involved in cortical astrocyte dopamine uptake are the norepinephrine transporter and plasma membrane monoamine transporter. Both dopamine receptor subtypes were identified in cortical astrocyte cultures. 24-hour treatment of astrocyte cultures with apomorphine, a D1/D2 agonist, induced upregulation of D1 receptor, norepinephrine transporter and plasma membrane monoamine transporter, whereas the latter was downregulated by haloperidol and L-DOPA. Astrocytes take up dopamine by multiple transporters and express dopamine receptors, which are sensitive to dopaminergic drugs. The findings of this study could open a promising area of research for the fine-tuning of existing therapeutic strategies.
01 Sep 2023Submitted to European Journal of Neuroscience
02 Sep 2023Submission Checks Completed
02 Sep 2023Assigned to Editor
03 Sep 2023Review(s) Completed, Editorial Evaluation Pending
03 Sep 2023Reviewer(s) Assigned
03 Nov 20231st Revision Received
03 Nov 2023Submission Checks Completed
03 Nov 2023Assigned to Editor
03 Nov 2023Review(s) Completed, Editorial Evaluation Pending
11 Nov 2023Editorial Decision: Accept