Intracerebroventricular injection of antibodies directed against Gs alpha enhances the supraspinal antinociception induced by morphine, beta-endorphin and clonidine in mice.
The intracerebroventricular (i.c.v.) injection of antisera directed against different sequences of Gs alpha to mice enhanced the antinociceptive potency of the opioids morphine, beta h-endorphin-(1-31) and of the alpha 2-agonist clonidine when studied 24 h later in the tail-flick test. The activity of DAGO, DADLE, DPDPE and [D-Ala2]-Deltorphin II remained unchanged after that treatment. Cholera toxin (0.5 microgram/mouse, i.c.v.), agent that impairs the receptor regulation of Gs transducer proteins promoted comparable changes in the supraspinal analgesia induced by these substances. Six days after a single i.c.v. injection (0.5 microgram/mouse) of pertussis toxin the antinociceptive activity of all the opioids and clonidine appeared diminished. It is concluded that opioids and clonidine promote analgesia after binding to receptors functionally coupled to Gi/G(o) proteins, moreover, the activity of morphine, beta-endorphin and clonidine in this test seems to be counteracted by a process involving activation of Gs alpha transducer proteins.
Sánchez-Blázquez
P
P
Neuropharmacology Unit, Cajal Institute, C.S.I.C., Madrid, Spain.
Garzón
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D002772:Cholera Toxin / Q000008:administration & dosage; D003000:Clonidine / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000276:immunology*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009020:Morphine / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects*; D010147:Pain Measurement / Q000187:drug effects; D011817:Rabbits; D013116:Spinal Cord / Q000502:physiology; D001615:beta-Endorphin / Q000494:pharmacology*
D000906:Antibodies; D001615:beta-Endorphin; D009020:Morphine; D002772:Cholera Toxin; D019204:GTP-Binding Proteins; D003000:Clonidine