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

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Abstract
High 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]enkephalin (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.