Reconstitution of rat brain mu opioid receptors with purified guanine nucleotide-binding regulatory proteins, Gi and Go.

Abstract

Reconstitution of purified i opioid receptors with purified guanine nucleotide-binding regulatory proteins

Subgroups among μ‐opioid receptor agonists distinguished by ATP‐sensitive K+ channel‐acting drugs

“…morphine, a predominantly IA2-mediated effect (Heyman et al, 1988;Pick et al, 1993), are both antagonized by the KATP channel blocker, glibenclamide (Narita et al, 1992a;Welch & Dunlow, 1993). In addition, the antinociception elicited by the peripheral administration of morphine and fentanyl is due mostly to activation of #i, receptors (Ling et al, 1985;Jang & Yoburn, 1991) (Ueda et al, 1988;1990).…”

Evidence for receptor‐mediated inhibition of intrinsic activity of GTP‐binding protein, Gi1 and Gi2, but not G0 in reconstitution experiments

“…However, we have not yet obtained data about the xreceptor-mediated changes in GTPase activity per se ('turn off' reaction). Taking into account that most of G-protein-coupled receptors mediate the stimulation of the intrinsic activities of G-protein [1][2][3], the present finding may be the first evidence for receptor-mediated inhibition of G-protein activity in signal transduction mechanisms through plasma membranes. Experimental support for this conclusion is as follows.…”

“…The activation of Gproteins is terminated by the hydrolysis of GTP to GDP (or Pi release) due to the low-Kra (high affinity) GTPase activity inherent in the G-protein a-subunits. Thus, the agonist-mediated increase in low-Kin GTPase activity is accepted as a secondary event to increase in GDP-GTP exchange [2,3].…”

A subtype of opioid κ‐receptor is coupled to inhibition of Gil‐mediated phospholipase C activity in the guinea pig cerebellum

“…Alternatively it might be explained by the possibility that fly subunits released from Gi or abundant Go activated by GTP per se immediately trap the a-subunits released to a small extent from Gq/ll/16 by GTP per se or unintentionally activated receptors. Indeed, Go is not only most abundantly found in the brain among many heterotrimeric G-proteins, but also its intrinsic activity (GTPase or GDP-GTP exchange activity) is the highest [32]. Furthermore Goa has no activity to activate PLC in the Xenopus oocyte, since evoked currents through 8-opioid receptor which is coupled to Go in neuroblastoma X glioma hubrid NG108-15 cells [33], were not mediated by overexpression of Goa [11].…”