Biomedical subjects

Guo-Xi Xie

Publications and source records attributed to Guo-Xi Xie.

7 recordsLinked to original sources

PubMed2006

How regulators of G protein signaling achieve selective regulation.

The regulators of G protein signaling (RGS) are a family of cellular proteins that play an essential regulatory role in G protein-mediated signal transduction. There are multiple RGS subfamilies consisting of over 20 different RGS proteins. They are basically the guanosine triphosphatase (GTPase)-accelerating proteins that specifically interact with G protein alpha subunits. RGS proteins display remarkable selectivity and specificity in their regulation of receptors, ion channels, and other G protein-mediated physiological events. The molecular and cellular mechanisms underlying such selectivity are complex and cooperate at many different levels. Recent research data have provided strong evidence that the spatiotemporal-specific expression of RGS proteins and their target components, as well as the specific protein-protein recognition and interaction through their characteristic structural domains and functional motifs, are determinants for RGS selectivity and specificity. Other molecular mechanisms, such as alternative splicing and scaffold proteins, also significantly contribute to RGS selectivity. To pursue a thorough understanding of the mechanisms of RGS selective regulation will be of great significance for the advancement of our knowledge of molecular and cellular signal transduction.

Animals↗

PubMed2005

N-terminally truncated variant of the mouse GAIP/RGS19 lacks selectivity of full-length GAIP/RGS19 protein in regulating ORL1 receptor signaling.

The regulators of G protein signaling (RGS) are a family of proteins with conserved RGS domains and play essential roles in regulating G protein-mediated signal transduction and physiological events. GAIP/RGS19 (G alpha interacting protein, also classified as RGS19), a member of the RGS family, has been shown to negatively regulate the signaling of many G protein-coupled receptors, including the opioid receptors. Two GAIP/RGS19 mRNA variants, resulted from an alternative splicing of exon 2 of the GAIP/RGS19 gene, were identified in multiple mouse tissues. One of the transcripts consists of a complete set of exons and encodes a full-length GAIP/RGS19 protein, and the other does not have exon 2 and therefore encodes an N-terminal 22 residue truncated short GAIP/RGS19 protein. When co-expressed with either the opioid-receptor-like (ORL1) receptor or one of the mu, delta, and kappa opioid receptors, by transfecting dual-expression plasmids into COS-7 cells, the full-length GAIP/RGS19 was more effective than the N-terminally truncated variant and was more selective in regulating the ORL1 receptor signaling than in regulating the mu, delta, and kappa opioid receptors, as measured by the effectiveness to increase the agonist-stimulated GTPase activity and to reverse the agonist-induced inhibition of cyclic AMP accumulation. In the same assays, the N-terminally truncated GAIP/RGS19 did not distinguish ORL1 from the mu, delta, and kappa opioid receptors. In contrast, co-expression of RGS4 with either ORL1 or opioid receptors showed the selectivity of RGS4 for regulating opioid receptors was mu > kappa > delta > ORL1, an order completely different from that of GAIP/RGS19. The results suggest that GAIP/RGS19 prefers regulating ORL1 receptor signaling over other opioid receptors, and that the N-terminal domain of GAIP/RGS19 plays a crucial role in its receptor preference.

Alternative Splicing↗

PubMed2005

RGS proteins: new players in the field of opioid signaling and tolerance mechanisms.

In this article we review recent advances in our understanding of the crucial role of the Regulator of G protein Signaling (RGS) proteins in opioid signaling mechanisms and opioid tolerance development. Opioids exert their physiologic effects via complex G protein-coupled receptor-signaling mechanisms, and RGS proteins are now known to tightly regulate the G protein signaling cycle. RGS proteins contain GTPase-accelerating protein activity within their characteristic RGS domain and various other receptor signaling-related properties of their other functional domains. There have been more than 20 RGS proteins reported in the literature, and multiple RGS proteins have been shown to negatively regulate G protein-mediated opioid signaling, facilitate opioid receptor desensitization and internalization, and affect the rate at which opioid tolerance develops. Using RGS proteins as targets for future drug therapy aimed at modulating opioid effectiveness in both acute and chronic pain settings may be an important advance in the treatment of pain.

Analgesics, Opioid↗

PubMed2005

Age-dependent morphine tolerance development in the rat.

In all age groups, the use of opioids to treat chronic pain conditions has increased, yet the impact of age on opioid tolerance development has not been comprehensively addressed. In this study, we investigated age-related differences in morphine tolerance development in rats. Rats aged 3 wk, 3 mo, 6 mo, and 1 yr were used in the study. Morphine (8 mg/kg) was injected subcutaneously twice each day and its analgesic effect assessed by the change in tail-flick latency using a thermal stimulus 5 min before and 30 min after dosing. Tolerance was defined as a 75% reduction in morphine-induced analgesia compared to Day 1. Rats aged 3 wk, 3 mo, 6 mo, and 1 yr developed tolerance on the 4th, 10th, 14th, and 22nd days of morphine treatment, respectively. Plasma levels of morphine and its metabolites showed that pharmacokinetic differences among the groups did not correlate with the differences in tolerance development. This study demonstrates that morphine tolerance occurs more rapidly in younger rats than older rats and is unlikely to be the result of differences in drug metabolism or clearance. Aging may impact molecular processes involved in tolerance development and provide insight into novel therapeutic targets to delay opioid tolerance development.

Aging↗

PubMed2003

Local anesthetics differentially inhibit sympathetic neuron-mediated and C fiber-mediated synovial neurogenic plasma extravasation.

UNLABELLED: Local anesthetics are used for local irrigation after many types of operations. However, recent evidence of toxic effects of local anesthetics at large concentrations during continuous administration suggests an advantage of using decreased local anesthetic concentrations for irrigation solutions. In this study, we determined whether smaller concentrations of local anesthetics may maintain an antiinflammatory and, therefore, analgesic effect without the risk of possible toxicity. Lidocaine and bupivacaine were studied for their ability to inhibit both components of neurogenic inflammation-C fiber-mediated and sympathetic postganglionic neuron (SPGN)-mediated inflammation-in the rat knee joint. Intraarticular lidocaine 0.02% reduced 5-hydroxytryptamine (5-HT)-induced (SPGN-mediated) plasma extravasation (PE) by 35%, and further decreases were obtained by perfusing larger concentrations of lidocaine. Intraarticular bupivacaine 0.025% inhibited 5-HT-induced PE by 60%, and a 95% inhibition was obtained with bupivacaine 0.05%. Larger local anesthetic concentrations were necessary to inhibit C fiber-mediated PE than those required to inhibit SPGN-mediated PE. Lidocaine 0.4% was required to reduce mustard oil-induced PE by 60%. Lidocaine 2% inhibited mustard oil-induced PE to baseline levels. Bupivacaine 0.1% was required for an 80% reduction of PE. Bupivacaine 0.25% inhibited mustard oil-induced PE to baseline levels. Our results demonstrate differential effects of local anesthetics on SPGN- and C fiber-mediated PE but confirm the concept of using smaller concentrations of local anesthetics to achieve inhibition of postoperative inflammation. IMPLICATIONS: Local anesthetic wound irrigation is often used to treat postoperative surgical pain. Large concentrations of local anesthetics are usually used, and these concentrations may have possible neurotoxic and myotoxic effects. Our results demonstrate antiinflammatory effects of lidocaine and bupivacaine at concentrations smaller than used clinically.

Anesthetics, Local↗

PubMed2002

5-HT7 receptors are involved in mediating 5-HT-induced activation of rat primary afferent neurons.

The purpose of this study was to determine whether the 5-hydroxytryptamine7 (5-HT7) receptor is expressed by nociceptor-like neurons in the rat PNS and whether 5-HT activates these nociceptors via the 5-HT7 receptor subtype. Using a polyclonal antibody and the method of immunofluorescence staining, we demonstrated that the 5-HT7 receptor appears predominately on "nociceptor-like" neurons of the rat lumbar dorsal root ganglia. Using immunocytochemical methods, we showed that the immunoreactivity of the 5-HT7 receptor antibody complex is localized in the superficial layers of the spinal cord dorsal horn, which corresponds with laminae I, IIouter and IIinner. Furthermore, we demonstrated that noxious stimulation produced by knee injection of 5-HT or a 5-HT7 agonist dose-dependently increases c-Fos production of the rat spinal cord dorsal horn. This effect was significantly inhibited by the preinjection of a 5-HT7 antagonist. We conclude that the 5-HT7 receptor is expressed by rat primary afferent nociceptors which terminate in the superficial layers of the spinal cord dorsal horn and that the 5-HT7 receptor subtype is involved in nociceptor activation by 5-HT.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1984

Dynorphin: important mediator for electroacupuncture analgesia in the spinal cord of the rabbit.

Intrathecal injection of 12 nmol of dynorphin elicited marked analgesia as measured by tail flick latency, the effect being about 20 times more potent than with morphine. This analgesic effect could be reversed by naloxone at a dose 1.5-fold higher than that needed to reverse morphine analgesia. Intrathecal injection of anti-dynorphin antibody blocked electroacupuncture (EA) analgesia by 77%, the effect lasting for at least 4 h. In rabbits made tolerant to EA analgesia by long-term EA stimulation, intrathecal injection of dynorphin no longer exhibited an analgesic effect. No analgesia was noticed when dynorphin (10 nmol) was injected into the periaqueductal grey (PAG) of the rabbit, nor was EA analgesia blocked by anti-dynorphin antibody injected into PAG. These results suggest that dynorphin reduces nocifensive responses in the spinal cord and may play an important role in mediating EA analgesia at the spinal level.

Acupuncture Therapy↗