Adenosine Receptors Differentially Regulate the Expression of Regulators of G-Protein Signalling (RGS) 2, 3 and 4 in Astrocyte-Like Cells

Abstract

The “regulators of g-protein signalling” (RGS) comprise a large family of proteins that limit by virtue of their GTPase accelerating protein domain the signal transduction of G-protein coupled receptors. RGS proteins have been implicated in various neuropsychiatric diseases such as schizophrenia, drug abuse, depression and anxiety and aggressive behaviour. Since conditions associated with a large increase of adenosine in the brain such as seizures or ischemia were reported to modify the expression of some RGS proteins we hypothesized that adenosine might regulate RGS expression in neural cells. We measured the expression of RGS-2,-3, and -4 in both transformed glia cells (human U373 MG astrocytoma cells) and in primary rat astrocyte cultures stimulated with adenosine agonists. Expression of RGS-2 mRNA as well as RGS2 protein was increased up to 30-fold by adenosine agonists in astrocytes. The order of potency of agonists and the blockade by the adenosine A2B-antagonist MRS1706 indicated that this effect was largely mediated by adenosine A2B receptors. However, a smaller effect was observed due to activation of adenosine A2A receptors. In astrocytoma cells adenosine agonists elicited an increase in RGS-2 expression solely mediated by A2B receptors. Expression of RGS-3 was inhibited by adenosine agonists in both astrocytoma cells and astrocytes. However while this effect was mediated by A2B receptors in astrocytoma cells it was mediated by A2A receptors in astrocytes as assessed by the order of potency of agonists and selective blockade by the specific antagonists MRS1706 and ZM241385 respectively. RGS-4 expression was inhibited in astrocytoma cells but enhanced in astrocytes by adenosine agonists.

Eph/ephrin signalling serves a bidirectional role in lipopolysaccharide‑induced intestinal injury

“…In contrast, in cortical interneurons binding of EphB1 to Ephrin B3 would enhance the phosphorylation of Src ( 29 ). Consistent with our data, it has been demonstrated that the activation of EphrinB-dependent ‘reverse’ signalling could downregulate β-catenin level in the cytoplasm by recruiting Axin protein, but in the meantime Wnt signalling could also suppress the EphB-ephrinB pathway by inhibiting the transcription of ephrinB ligands ( 30 ). Therefore, we hypothesised that the maladjustment of negative feedback loops between EphrinB-dependent ‘reverse’ signalling and the Wnt/β-catenin pathway might act as a crucial factor which influenced the excessive activation of the EphA2-Ephrin A1 pathway and led to LPS-induced persistent inflammation and injury.…”

Top Common Differentially Expressed Genes in the Epileptogenic Nucleus of Two Strains of Rodents Susceptible to Audiogenic Seizures: WAR and GASH/Sal

“…Increased levels of Rgs2 transcripts were also observed in the prefrontal cortex and hippocampus of rats following an acute electroconvulsive stimulation and were normalized 24 h later (49). Such fluctuations in mRNA expression levels of Rgs2 were suggested as an adaptation of neurons in an attempt to reduce cell depolarization and the probability of new epileptiform events (49), mainly because RGS2 indirectly modulates calcium channels (50,51). Christensen et al (52) also reported an increased expression of Rgs2 in the hippocampus of kindled rats after electroconvulsive stimulation, showing that transcript levels of this gene were reduced after Levetiracetam treatment.…”

Inflammation-associated regulation of RGS in astrocytes and putative implication in neuropathic pain

“…Several studies have highlighted the role of reactive glial cells in neuropathic pain but the expression of RGS in these cells remains so far poorly investigated [ 51 , 52 ]. The expression of RGS in astrocytes and their regulation was herein examined in primary cultures exposed to selected conditions in which cells adopt typical characteristics of reactive astrocytes [ 53 – 56 ].…”