Opioids binding mu and delta receptors exhibit diverse efficacy in the activation of Gi2 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 Gi2/ G(x/z) transducer proteins of mouse periaqueductal gray matter membranes. In the presence of picomolar concentrations of guanosine 5'-O-(3-thiotriphosphate), the opioid agonists promoted concentration-dependent increases of immunoreactivity associated with free Gi2alpha and G(x/z)alpha subunits. [D-Ala2,N-MePhe4, Gly-ol5]enkephalin and morphine (preferential agonists at mu opioid receptors) and beta-endorphin-(1-31) (an agonist at mu/delta opioid receptors) activated G(x/z) proteins. In contrast, the agonists of delta opioid receptors, [D-Ala2]deltorphin II and [D-Pen(2,5)]enkephalin, displayed little or no activity on this pertussis toxin resistant regulatory protein. Although exhibiting diverse efficacy, all the opioids studied activated Gi2 transducer proteins. [D-Ala2,N-MePhe4,Gly-ol5]enkephalin and [D-Ala2]-deltorphin II were more potent at Gi2alpha subunits than at G(x/z)alpha subunits. The opioid antagonist naloxone displayed a competitive profile in reducing the activation of G proteins promoted by morphine. Moreover, [D-Pen(2,5)]enkephalin antagonized the releasing effect exerted by [D-Ala2]deltorphin II on Gi2alpha and G(x/z)alpha subunits. N,N-diallyl-Tyr-Aib-Aib-Phe-Leu (ICI-174864) reduced the G alpha-related immunosignals promoted by agonists of delta opioid receptors. Therefore, it is suggested that opioids exhibit marked differences in efficacy and/or potency in the activation of Gi2 and G(x/z) transducer proteins in mouse periaqueductal gray matter.