title: Gx/z is regulated by mu but not delta opioid receptors in the stimulation of the low Km GTPase activity in mouse periaqueductal grey matter.
abstract: High affinity low K(m) GTPase activity was measured in membrane preparations of adult mouse mesencephalic periaqueductal grey matter (PAG). Opioids displaying selectivity towards mu- or delta-opioid receptors (OR) activated the enzyme in a concentration-dependent manner. Antibodies to mu-OR greatly impaired the potential of mu-agonists, [D-Ala2,N-MePhe4,Gly-ol5]-enkephalin (DAMGO) and morphine, to increase hydrolysis of GTP. The same antibodies had little effect on [D-Pen2,5]enkephalin (DPDPE) and [D-Ala2]deltorphin II, both agonists at delta-OR. Stimulation of GTPase by DPDPE and [D-Ala2]deltorphin II - but not by morphine or DAMGO - was diminished by antibodies to delta-OR. The blockade of G(i2)alpha subunits by specific antibodies impaired the activation of G alpha-related GTPase by all opioids. Antibodies in vitro, and oligodeoxynucleotides in vivo, prepared against Gx/z alpha subunits, reduced the release of Pi promoted by DAMGO and morphine. The impairment of Gx/z proteins also slightly reduced the effect of the delta2 agonist [D-Ala2]deltorphin II. At delta1 receptors, DPDPE fully expressed its activation of GTPase. These results indicate that in the PAG, mu-OR and delta-OR couple with Gi2 transducer proteins. Notably, mu-OR also regulates the pertussis toxin-insensitive G-protein Gx/z, an effect poorly exhibited by delta-OR in this tissue.
authors.affiliation: Neurofarmacología, Instituto Cajal, CSIC, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Garzón
authors.forename: Y
authors.initials: Y
authors.lastname: Martínez-Peña
authors.forename: P
authors.initials: P
authors.lastname: Sanchez-Blázquez
mesh_terms: D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000502:physiology*; D007120:Immunochemistry; D007276:Injections, Intraventricular; D007700:Kinetics; D008297:Male; D051379:Mice; D009841:Oligonucleotides; D009842:Oligopeptides / Q000494:pharmacology; D010487:Periaqueductal Gray / Q000201:enzymology / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000502:physiology*; D013268:Stimulation, Chemical
chemical_list: D004745:Enkephalins; D009841:Oligonucleotides; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C059567:deltorphin; D020881:Enkephalin, D-Penicillamine (2,5)-; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins