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.
Garzón
J
J
Neurofarmacología, Instituto de Neurobiología Santiago Ramón y Cajal,Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
García-España
A
A
Sánchez-Blázquez
P
P
D000595:Amino Acid Sequence; D000818:Animals; D004305:Dose-Response Relationship, Drug; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007122:Immunoelectrophoresis; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D017465:Receptors, Opioid, delta / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000502:physiology*
D004745:Enkephalins; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D020881:Enkephalin, D-Penicillamine (2,5)-; D019204:GTP-Binding Proteins