THE DELTA2-OPIOID RECEPTOR SUBTYPE STIMULATES PHOSPHOINOSITIDE METABOLISM IN MOUSE PERIAQUEDUCTAL GRAY MATTER

Abstract The delta(δ)-opioid agonists [D-Pen 2,5 ]enkephalin (DPDPE) and [D-Ala 2 ]deltorphin II increased the formation of inositol phosphates (IPs) in mice periaqueductal gray matter (PAG) slices pre-labeled with myo - 3 H]inositol. Both δ-agonists caused an increase in IP accumulation in a dose-dependent manner (1–100 μM) and which was pertussis toxin (0.5 μg/mouse, icv) sensitive. This effect was blocked by the δ-antagonist ICI-174.864 (10 μM). The presence of subtypes of the δ-opioid receptor ( δ 1 and δ 2 ) in PAG has been suggested by pharmacological studies. In this brain structure, naltrindrole 5′-isothiocyanate (5′-NTII), but not 7-benzylidenenaltrexone (BNTX), antagonized the effects of DPDPE and [D-Ala 2 ]deltorphin II, suggesting the involvement of a population of delta receptors sensitive to the δ 2 -antagonist NT II on this effect. To further investigate the participation of δ-receptor subtypes in the stimulation of IPs formation, mice were injected with antisense oligodeoxynucleotides (ODNs) directed to nucleotides 7–26 or 29–46 of the cloned δ-receptor mRNA, and PAG slices from these animals were used in in vitro assays. The results demonstrate that the reported increase of phosphoinositide (PI) hydrolysis depends on the agonist activation of the δ 2 -opioid receptor Subtype in the PAG.