Expression of Neural RGS-R7 and Gβ5 Proteins in Response to Acute and Chronic Morphine

Abstract

The R7 subfamily of regulators of G-protein signaling (RGS) proteins (RGS6, RGS7, RGS9-2, and RGS11), and its binding protein Gb5, are found in neural structures of mouse brain. A single intracerebroventricular priming dose of 10 nmol morphine gave rise to acute tolerance to the analgesic effects of successive identical test doses of the opioid. At 2 h after administering the acute opioid, RGS7 mRNA levels in the striatum plus those of RGS9-2 in the striatum and thalamus were increased, whereas RGS9-2 and RGS11 mRNA were reduced in the cortex. Similar but attenuated RGS-R7 mRNA changes persisted 24 h after acute morphine administration. No changes in Gb5 mRNA levels were observed. At 2 days after commencing sustained morphine treatment, the levels of mRNA for RGS7, RGS9-2, RGS11, and Gb5 increased in most of the brain structures studied (striatum, thalamus, periaqueductal gray matter (PAG), and cortex). In these morphine tolerant-dependent mice, the greater changes were found for RGS9-2 in the thalamus (4500%) and PAG (4200%). In post-dependent mice, the increases in RGS-R7 and Gb5 mRNA still persisted in the PAG and striatum at 8 and 16 days after starting the chronic opioid treatment. The raised mRNA levels promoted by chronic, but not by acute, morphine, were accompanied by increases in the encoded proteins. This is probably a result of the costabilization of the RGS-R7 and Gb5 proteins forming heterodimers. Opioidinduced adaptations of RGS-R7 and Gb5 genes may regulate the severity of morphine-induced tolerance/dependence and the duration of the post-dependent period, helping to recover the normal response.

Activation of μ-Opioid Receptors Transfers Control of Gα Subunits to the Regulator of G-protein Signaling RGS9-2

“…1C). Although, in the mouse, the 77-kDa RGS9-2 protein is found in large amounts in striatal membranes, it is also present in other neural structures such as the cerebral cortex and PAG (7,23,30). The antibody directed against the RGS9-2 N-terminal sequence gave more intense signals than that directed against the C-terminal domain (Fig.…”

Interaction between the <i>RGS6</i> gene and psychosocial stress on obesity-related traits

“…This consistent result may be critical to apply our significant findings to Korean general population. RGS6 belongs to the R7 subfamily of RGS (regulator of G-protein signaling) family, which is widely expressed in multiple tissues including ovarian, bladder, and brain [13,14]. In particular, in tissues of the central nervous system such as the spinal cord and pons-medulla, RGS6 shows the highest mRNA expression levels [14].…”

“…RGS6 belongs to the R7 subfamily of RGS (regulator of G-protein signaling) family, which is widely expressed in multiple tissues including ovarian, bladder, and brain [13,14]. In particular, in tissues of the central nervous system such as the spinal cord and pons-medulla, RGS6 shows the highest mRNA expression levels [14]. This gene plays an important role in signaling by opioid effects which involves a negative feedback mechanism, acting downstream of opioid receptors to produce tachyphylaxis and acute tolerance [14].…”

“…In particular, in tissues of the central nervous system such as the spinal cord and pons-medulla, RGS6 shows the highest mRNA expression levels [14]. This gene plays an important role in signaling by opioid effects which involves a negative feedback mechanism, acting downstream of opioid receptors to produce tachyphylaxis and acute tolerance [14]. Severe psychosocial stress causes an elevated cortisol level and it promotes consumption of sweet, fatty, and calorie-dense "comfort food".…”

Roles for Regulator of G Protein Signaling Proteins in Synaptic Signaling and Plasticity

“…RGS7 is found throughout the brain (Khawaja et al, 1999), with reports indicating dense mRNA expression in the cerebellum, hypothalamus, and thalamus (Lopez-Fando et al, 2005), and mRNA and protein expression in hippocampus (Shelat et al, 2006; Fajardo-Serrano et al, 2013) and striatum (Larminie et al, 2004;Anderson et al, 2009) (Table 1). Within the hippocampus, RGS7 is found mostly extrasynaptically in dendrites at asymmetric (primarily excitatory) synapses (Fajardo-Serrano et al, 2013), with Gb5 regulating the cellular distribution of RGS7 (Rose et al, 2000).…”