OPIOIDS BINDING MU-RECEPTORS AND DELTA-RECEPTORS EXHIBIT DIVERSE EFFICACY IN THE ACTIVATION OF G(I2) AND G(X Z) TRANSDUCER PROTEINS IN MOUSE PERIAQUEDUCTAL GRAY-MATTER/

A nonisotopic, immunoelectrophoretic technique was used to analyze the characteristics of opioid-evoked activation of G(i2)/G(x/z) transduce r proteins of mouse periaqueductal gray matter membranes. In the prese nce of picomolar concentrations of guanosine 5'-O-(3-thiotriphosphate) , the opioid agonists promoted concentration-dependent increases of im munoreactivity associated with free G(i2 alpha) and G(x/z alpha) subun its. [D-Ala(2),N-MePhe(4), Gly-ol(5)]enkephalin and morphine (preferen tial agonists at mu opioid receptors) and beta-endorphin-(1-31) (an ag onist at mu/delta opioid receptors) activated G(x/z) proteins. In cont rast, the agonists of delta opioid receptors, [D-Ala(2)]deltorphin II and [D-Pen(2,5)]enkephalin, displayed little or no activity on this pe rtussis toxin resistant regulatory protein. Although exhibiting divers e efficacy, all the opioids studied activated G(i2) transducer protein s. [D-Ala(2),N-MePhe(4),Gly-ol(5)]enkephalin and [D-Ala(2)]deltorphin II were more potent at G(i2)alpha subunits than at G(x/z)alpha subunit s. The opioid antagonist naloxone displayed a competitive profile in r educing the activation of G proteins promoted by morphine. Moreover, [ D-Pen(2,5)]enkephalin antagonized the releasing effect exerted by [D-A la(2)]deltorphin II on G(i2)alpha and G(x/z)alpha subunits. N,N-dially l-Tyr-Aib-Aib-Phe-Leu (ICI-174864) reduced the G alpha-related immunos ignals promoted by agonists of delta opioid receptors. Therefore, it i s suggested that opioids exhibit marked differences in efficacy and/or potency in the activation of G(i2) and G(x/z) transducer proteins in mouse periaqueductal gray matter.