Pharmacological and molecular evidence for dopamine D1 receptor expression by striatal astrocytes in culture

Abstract

The neurotransmitter dopamine (DA) at a 10 microM concentration elicited a stimulation of intracellular cyclic AMP (cAMP) accumulation in cultured astrocytes derived from embryonic rat striatum. This accumulation was partially blocked by the beta-adrenergic receptors antagonist propranolol, mimicked by the D(1) agonist SKF 38393 and by the mixed D(1)/D(2) agonist apomorphine. A regional heterogeneity in the magnitude of dopamine-induced cAMP accumulation was observed in cultured astrocytes obtained from different brain areas. The maximum effect was observed in striatal astrocytes, a lower effect in cortical astrocytes, and no increase was detected in cerebellar astrocytes. Reverse transcription-polymerase chain reaction (RT-PCR) coupled to Southern blot hybridization demonstrated that striatal astrocytes express only D(1) receptor mRNA and Western blot analysis confirmed the expression of the D(1) receptor protein in striatal astrocytes. In contrast to what found in neurons, the D(1)-dependent cAMP formation in striatal astrocytes is partially reduced by pertussis toxin (PTX) treatment. The stimulation of D(1) receptors or the activation of adenylyl cyclase by forskolin led to an increase of cytosolic and nuclear protein kinase A (PKA) catalytic activity. The presence of dopamine D(1) receptors in cultured striatal astrocytes suggests a role of dopamine in the regulation of cellular processes in striatal astrocytes.

Neuronal A1 receptors mediate increase in extracellular kynurenic acid after local intrastriatal adenosine infusion

“…Thus, stimulation of A 1 receptors, but not A 2A receptors (Sebastiao and Ribeiro 1996), inhibits the release of glutamate (Fredholm 1995) and decreases the extracellular levels of dopamine (Zetterström and Fillenz 1990;Ballarin et al 1995;Okada et al 1996), acetylcholine (Bueters et al 2003), and GABA (Ferré et al 1996). Adenosine-induced reductions in these or other intercellular messenger substances could in turn affect glial KYNA synthesis by impairing the signaling of distinct astrocytic membrane receptors (Steinhäuser et al 1994;Zanassi et al 1999;Khan et al 2001;Sharma and Vijayaraghavan 2001;Zhou and Kimelberg 2001;Araque et al 2002). In this hypothetical scenario, downstream events within astrocytes will subsequently stimulate KYNA synthesis and thus cause an increase in extracellular KYNA levels (Fig.…”

Regulation of Glutamate Carboxypeptidase II Function in Corticolimbic Regions of Rat Brain by Phencyclidine, Haloperidol, and Clozapine

“…Increasing evidence indicates that astrocytes express receptors for nearly every neurotransmitter class (Coyle and Schwarcz, 2000), including functional D 2 and D 1 dopamine receptors (Bal et al, 1994;Zanassi et al, 1999;Reuss et al, 2000) and 5-HT2A receptors (Hagberg et al, 1998;Hirst et al, 1998). Thus, it is possible that neuroleptics act directly on receptors on astrocytes.…”

Thinking Outside the Cleft to Understand Synaptic Activity: Contribution of the Cystine-Glutamate Antiporter (System xc−) to Normal and Pathological Glutamatergic Signaling

“…SYSTEM X C Ϫ AND DISEASE Guidetti et al, 2007;Kucukdereli et al, 2011). In turn, astrocytes monitor neuronal activity through the expression of receptors activated by virtually every major neurotransmitter including glutamate, GABA, monoamines, acetylcholine, and endocannabinoids (Bormann and Kettenmann, 1988;Sontheimer et al, 1988;Glaum et al, 1990;Pruss et al, 1991;von Blankenfeld and Kettenmann, 1991;Wyllie et al, 1991;Zanassi et al, 1999;Grybko et al, 2010;Navarrete and Araque, 2010;Shen and Yakel, 2012). Because astrocytes have primarily nonoverlapping domains and may contact more than a million synapses (in the human cortex) (Bushong et al, 2002(Bushong et al, , 2004Ogata and Kosaka, 2002;Oberheim et al, 2006), these cells are in a position to coordinate activity on a network level.…”