GX Z IS REGULATED BY MU BUT NOT DELTA-OPIOID RECEPTORS IN THE STIMULATION OF THE LOW K-M GTPASE ACTIVITY IN MOUSE PERIAQUEDUCTAL GREY-MATTER/

High affinity low K-m GTPase activity was measured in membrane prepara tions of adult mouse mesencephalic periaqueductal grey matter (PAG). O pioids displaying selectivity towards mu- or delta-opioid receptors (O R) activated the enzyme in a concentration-dependent manner. Antibodie s to mu-OR greatly impaired the potential of mu-agonists, [D-Ala(2),N- MePhe(4),Gly-ol(5)]-enkephalin (DAMGO) and morphine, to increase hydro lysis of GTP. The same antibodies had little effect an [D-Pen(2,5)]enk ephalin (DPDPE) and [D-Ala(2)]deltorphin II, both agonists at delta-OR , Stimulation of GTPase by DPDPE and [D-Ala(2)]deltorphin II - but not by morphine or DAMGO - was diminished by antibodies to delta-OR. The blockade of G(i2)alpha subunits by specific antibodies impaired the ac tivation of G alpha-related GTPase by all opioids. Antibodies in vitro , and oligodeoxynucleotides in vivo, prepared against Gx/z alpha subun its, reduced the release of Pi promoted by DAMGO and morphine. The imp airment of Gx/z proteins also slightly reduced the effect of the delta 2 agonist [D-Ala(2)]deltorphin II. At delta 1 receptors, DPDPE fully expressed its activation of GTPase. These results indicate that in the FAG, mu-OR and delta-OR couple with Gi2 transducer proteins. Notably, mu-OR also regulates the pertussis toxin-insensitive G-protein Gx/z, an effect poorly exhibited by delta-OR in this tissue.