Evidence Details for Oprd1
PMID Title Journal Year Abstract
23365600 Inhibition of Activity of GABA Transporter GAT1 by delta-Opioid Receptor. Evid Based Complement Alternat Med. 2012;2012:818451. doi: 10.1155/2012/818451. Epub 2012 Dec 25. 2012 Analgesia is a well-documented effect of acupuncture. A critical role in pain sensation plays the nervous system, including the GABAergic system and opioid receptor (OR) activation. Here we investigated regulation of GABA transporter GAT1 by deltaOR in rats and in Xenopus oocytes. Synaptosomes of brain from rats chronically exposed to opiates exhibited reduced GABA uptake, indicating that GABA transport might be regulated by opioid receptors. For further investigation we have expressed GAT1 of mouse brain together with mouse deltaOR and muOR in Xenopus oocytes. The function of GAT1 was analyzed in terms of Na(+)-dependent [(3)H]GABA uptake as well as GAT1-mediated currents. Coexpression of deltaOR led to reduced number of fully functional GAT1 transporters, reduced substrate translocation, and GAT1-mediated current. Activation of deltaOR further reduced the rate of GABA uptake as well as GAT1-mediated current. Coexpression of muOR, as well as muOR activation, affected neither the number of transporters, nor rate of GABA uptake, nor GAT1-mediated current. Inhibition of GAT1-mediated current by activation of deltaOR was confirmed in whole-cell patch-clamp experiments on rat brain slices of periaqueductal gray. We conclude that inhibition of GAT1 function will strengthen the inhibitory action of the GABAergic system and hence may contribute to acupuncture-induced analgesia."

Evidence Sentence: For further investigation we have expressed GAT1 of mouse brain together with mouse deltaOR and muOR in Xenopus oocytes.
Evidence Sentence: However, at a relatively high concentration, morphine could bind to all three opioid receptors, muOR, deltaOR, and kappaOR.
Evidence Sentence: In addition, a minor morphine metabolite, morphine-6-glucuronide, showed higher affinity to deltaOR and lower affinity to muOR, compared to that of morphine in rodents and human.
Evidence Sentence: While muOR is constitutively expressed at surface membrane, several studies have shown that the surface expression of deltaOR is regulated by inflammation, drug exposure, or stimulation.
Evidence Sentence: Notably, the physical interactions between muOR and deltaOR may contribute to long-term changes of morphine-induced analgesia.
Evidence Sentence: Therefore, we next examined the interaction between GAT1 and muOR or deltaOR using oocyte as a simplified and well-controlled system.
Evidence Sentence: Coinjection of 10 ng cRNA for the muOR instead of cRNA for deltaOR had no significant effect on the rate of GABA uptake (Figure 3(b)).
Evidence Sentence: Functional expression of deltaOR and muOR was confirmed in the absence of GAT1 activity by application of 100 nM of the deltaOR or muOR agonists, DPDPE or DAMGO, respectively, and by the resulting activation of the endogenous Ca2+-activated channels (data not shown, see also [30]); it is worth to mention that the voltage dependencies of the currents induced by DPDPE and DAMGO differ from each other indicating that different signaling pathways are activated.
Evidence Sentence: Figure 3(b) shows that activation of deltaOR by 100 nM DPDPE further reduced the rate of GABA uptake while activation of muOR by 100 nM DAMGO did not significantly change transport activity.
Evidence Sentence: Since the heterologous expression of GAT1 with deltaOR, but not muOR, exhibited significant effect on GABA uptake, we focused the rest of our study on deltaOR.
Evidence Sentence: We reasoned that the changes of either muOR or deltaOR signaling cascades might be responsible for acute and chronic morphine-induced GABA uptake inhibition.