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Gx/z is regulated by μ but not δ opioid receptors in the stimulation of the low Km GTPase activity in mouse periaqueductal grey matter

AuthorsGarzón, Javier
Issue Date1997
PublisherBlackwell Publishing
CitationEuropean Journal of Neuroscience 9: 1194- 1200 (1997)
AbstractHigh affinity low Km GTPase activity was measured in membrane preparations of adult mouse mesencephalic periaqueductal grey matter (PAG). Opioids displaying selectivity towards μ- or δ-opioid receptors (OR) activated the enzyme in a concentration-dependent manner. Antibodies to μ-OR greatly impaired the potential of μ-agonists, [D-Ala2,N-MePhe4,Gly-ol5]-enkephalin (DAMGO) and morphine, to increase hydrolysis of GTP. The same antibodies had little effect on [D-Pen2,5]enkeptialin (DPDPE) and [D-Ala2]deltorphin II, both agonists at δ-OR. Stimulation of GTPase by DPDPE and [D-Ala2]deltorphin II - but not by morphine or DAMGO - was diminished by antibodies to δ-OR. The blockade of Gi2α subunits by specific antibodies impaired the activation of Gα-related GTPase by all opioids. Antibodies in vitro, and oligodeoxynucleotides in vivo, prepared against Gx/zα subunits, reduced the release of Pi promoted by DAMGO and morphine. The impairment of Gx/z proteins also slightly reduced the effect of the δ2 agonist [D-Ala2]deltorphin II. At δ1 receptors, DPDPE fully expressed its activation of GTPase. These results indicate that in the PAG, μ-OR and δ-OR couple with Gi2 transducer proteins. Notably, μ-OR also regulates the pertussis toxin-insensitive G-protein Gx/z, an effect poorly exhibited by δ-OR in this tissue. © European Neuroscience Association.
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