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

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

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.

• Jezik: Angleški jezik
• Ključne besede: astrocytes, dopamine, rats, central nervous system, adult rat, cortical astrocytes, dopamine uptake, NET, PMAT
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2024
• Št. strani: Str. 1296–1310
• Številčenje: Vol. 59, iss. 6
• PID: 20.500.12556/RUL-155346
• UDK: 612
• ISSN pri članku: 1460-9568
• DOI: 10.1111/ejn.16202
• COBISS.SI-ID: 177881091
• Datum objave v RUL: 27.03.2024

Gradivo je del revije

• Naslov: European journal of neuroscience
• Skrajšan naslov: EJN, Eur. j. neurosci.
• Založnik: Wiley, Federation of European Neuroscience Societies
• ISSN: 1460-9568
• COBISS.SI-ID: 517706521

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: astrociti, dopamin, podgane, centralni živčni sistem

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P3-0067
• Naslov: Farmakologija in farmakogenomika

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Program financ.: Young researchers