Changes in regulator of G protein signaling-4 gene expression in the spinal cord of adrenalectomized rats in response to intrathecal morphine

Introduction: Regulators of G-protein signaling protein negatively control G protein -coupled receptor signaling duration by accelerating Gα subunit guanosine triphosphate hydrolysis. Since regulator of G-protein signaling4 has an important role in modulating morphine effects at the cellular level and the exact mechanism(s) of adrenalectomy-induced morphine sensitization have not been fully clarified, the present study was designed to determine the changes in the levels of RGS4 mRNA and protein in intact and adrenalectomized (ADX) morphine-treated rats. Materials and Methods: All experiments were carried out on male Wistar rats. The tail-flick test was used to assess the nociceptive threshold and corticosterone levels were measured by radioimmunoassay. The dorsal half of the lumbar spinal cord was assayed for the expression of RGS4 using semi-quantitative RT-PCR and immunoblotting. Results: Results showed that the anti-nociceptive effect of intrathecal morphine (5 μg) was significantly increased in ADX rats. The levels of RGS4 mRNA and protein in ADX rats were similar to those in intact animals. However, morphine could elicit a significant increase in both mRNA and protein levels of RGS4 following adrenalectomy. In contrast, the pattern of RGS4 gene expression did not show significant changes in the lumbar spinal cord of intact animals after morphine injection. Conclusion: Our results demonstrate that in the absence of corticosterone, morphine increases RGS4 through promoting its gene expression.