Stimulation of mu- and delta-opioid receptors enhances phosphoinositide metabolism in mouse spinal cord: evidence for subtypes of delta-receptors.
The accumulation of inositol phosphates (IPs) induced by agonist-activated opioid receptors was analysed in mouse spinal cord slices pre-labelled with myo-[3H]inositol. Agonists showing selectivity to mu-opioid receptors, morphine and [D-Ala2,MePhe4, Gly(ol)5]enkephalin (DAMGO), promoted concentration-dependent increases in the formation of IPs. The activation of delta-opioid receptors by the selective agonists [D-Pen2,5]enkephalin (DPDPE) and [D-Ala2]deltorphin II produced similar increases in phosphoinositide (PI) metabolism. Pre-treatment of the slices with pertussis toxin (PTX) blocked the effect of opioid agonists on IP production. The involvement of Gi/Go-protein (guanine nucleotide-binding protein) classes in this opioid effect is therefore suggested. The activity of the opioid agonists was reduced by the opioid antagonists naltrexone and naloxone. The antagonist at delta1-receptors, 7-benzylidenenaltrexone (BNTX), exhibited greater potency than the antagonists at delta2-receptors, naltriben methanesulphonate (NTB) or naltrindrole 5'-isothiocyanate (NT II), in reducing the activating effect of DPDPE on phosphoinositide metabolism. Conversely, NTB and NT II were more potent antagonists of the activity of [D-Ala2]deltorphin II than BNTX. This work demonstrates the coupling of spinal mu- and delta-opioid receptors to phospholipase C and the generation of IPs. It also provides biochemical evidence for pharmacological subtypes of delta-opioid receptors in the activation of this signalling pathway.
Sánchez-Blázquez
P
P
Neurofarmacología, Instituto Cajal, CSIC, Madrid, Spain.
Rodríguez-Díaz
M
M
Frejo
M T
MT
Garzón
J
J
D000818:Animals; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007536:Isomerism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009292:Narcotic Antagonists / Q000494:pharmacology; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007295:Inositol Phosphates; D009292:Narcotic Antagonists; D010716:Phosphatidylinositols; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin