Transporters involved in adult rat cortical astrocyte dopamine uptake : kinetics, expression and pharmacological modulation

Sočan, Vesna (author), Dolinar, Klemen (author), Kržan, Mojca (author)

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. Twenty-four-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.

• Language: English
• Keywords: astrocytes, dopamine, rats, central nervous system, adult rat, cortical astrocytes, dopamine uptake, NET, PMAT
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: Str. 1296–1310
• Numbering: Vol. 59, iss. 6
• PID: 20.500.12556/RUL-155346
• UDC: 612
• ISSN on article: 1460-9568
• DOI: 10.1111/ejn.16202
• COBISS.SI-ID: 177881091
• Publication date in RUL: 27.03.2024

Record is a part of a journal

• Title: European journal of neuroscience
• Shortened title: EJN, Eur. j. neurosci.
• Publisher: Wiley, Federation of European Neuroscience Societies
• ISSN: 1460-9568
• COBISS.SI-ID: 517706521

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: astrociti, dopamin, podgane, centralni živčni sistem

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0067
• Name: Farmakologija in farmakogenomika

• Funder: ARRS - Slovenian Research Agency
• Funding programme: Young researchers