THE DELTA(2)-OPIOID RECEPTOR SUBTYPE STIMULATES PHOSPHOINOSITIDE METABOLISM IN MOUSE PERIAQUEDUCTAL GRAY-MATTER

The delta(delta)-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 (FAG) slices pre-labeled with myo-[H-3]inositol. Both delta-agonists caused an increase in IP accumu lation in a dose-dependent manner (1-100 mu M) and which was pertussis toxin (0.5 mu g/mouse, icy) sensitive. This effect was blocked by the delta-antagonist ICI-174.864 (10 mu M). The presence of subtypes of t he delta-opioid receptor (delta(1) and delta(2)) in FAG has been sugge sted 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, suggesti ng the involvement of a population of delta receptors sensitive to the delta(2)-antagonist NT II on this effect. To further investigate the participation of delta-receptor subtypes in the stimulation of IPs for mation, mice were injected with antisense oligodeoxynucleotides (ODNs) directed to nucleotides 7-26 or 29-46 of the cloned delta-receptor mR NA, and FAG slices from these animals were used in in vitro assays. Th e results demonstrate that the reported increase of phosphoinositide ( PI) hydrolysis depends on the agonist activation of the delta(2)-opioi d receptor subtype in the FAG. (C) 1998 Elsevier Science Inc.