Vol. 281, Issue 1, 549-557, 1997

Opioids Binding Mu and Delta Receptors Exhibit Diverse Efficacy in the Activation of G_i2 and G_x/z Transducer Proteins in Mouse Periaqueductal Gray Matter¹

Javier Garzón, Antonio García-España and Pilar Sánchez-Blázquez

Neurofarmacología, Instituto de Neurobiología Santiago Ramón y Cajal, Consejo Superior de Investigaciones Científicas. Avenida Doctor Arce 37, 28002 Madrid, Spain

A nonisotopic, immunoelectrophoretic technique was used to analyze the characteristics of opioid-evoked activation of G_i2/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 G_i2 and G_x/z subunits. [D-Ala²,N-MePhe⁴,Gly-ol⁵]enkephalin and morphine (preferential agonists at mu opioid receptors) and -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 G_i2 transducer proteins. [D-Ala²,N-MePhe⁴,Gly-ol⁵]enkephalin and [D-Ala²]deltorphin II were more potent at G_i2 subunits than at G_x/z 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 G_i2 and G_x/z subunits. N,N-diallyl-Tyr-Aib-Aib-Phe-Leu (ICI-174864) reduced the G-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 G_i2 and G_x/z transducer proteins in mouse periaqueductal gray matter.