TY - JOUR T1 - Opioids Binding <em>Mu</em> and <em>Delta</em>Receptors Exhibit Diverse Efficacy in the Activation of G<sub>i2</sub>and G<sub>x/z</sub> Transducer Proteins in Mouse Periaqueductal Gray Matter JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 549 LP - 557 VL - 281 IS - 1 AU - Javier Garzón AU - Antonio García-España AU - Pilar Sánchez-Blázquez Y1 - 1997/04/01 UR - http://jpet.aspetjournals.org/content/281/1/549.abstract N2 - A nonisotopic, immunoelectrophoretic technique was used to analyze the characteristics of opioid-evoked activation of Gi2/Gx/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 Gi2α and Gx/zα subunits. [d-Ala2,N-MePhe4,Gly-ol5]enkephalin and morphine (preferential agonists at mu opioid receptors) and β-endorphin-(1–31) (an agonist atmu/delta opioid receptors) activated Gx/zproteins. In contrast, the agonists of delta opioid receptors, [d-Ala2]deltorphin II and [d-Pen2,5]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 Gi2α subunits than at Gx/zα subunits. The opioid antagonist naloxone displayed a competitive profile in reducing the activation of G proteins promoted by morphine. Moreover, [d-Pen2,5]enkephalin antagonized the releasing effect exerted by [d-Ala2]deltorphin II on Gi2α and Gx/zα subunits.N,N-diallyl-Tyr-Aib-Aib-Phe-Leu (ICI-174864) reduced the Gα-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 Gx/ztransducer proteins in mouse periaqueductal gray matter. The American Society for Pharmacology and Experimental Therapeutics ER -