PARTICIPATION OF DELTA-OPIOID RECEPTOR SUBTYPES IN THE STIMULATION OFADENYLYL-CYCLASE ACTIVITY IN RAT OLFACTORY-BULB

A number of recent investigations have proposed the existence of two p harmacologically distinct delta opioid receptor subtypes, named delta( 1) and delta(2). In the present study, we have investigated the involv ement of the two delta receptors in the opioid stimulation of adenylyl cyclase activity in rat olfactory bulb. In addition, we have conducte d a similar investigation in rat striatum, where delta agonists are kn own to inhibit cyclic AMP formation. Both (D-Ala(2), Glu(4)) deltorphi n (DELT), a delta(2) agonist, and [D-Pen(2), D-Pen(5)] enkephalin (DPD PE), a delta(1) agonist, stimulated adenylyl cyclase activity in rat o lfactory bulb in a conoentration-dependent manner, DELT being 25-fold more potent than DPDPE. The selective delta, antagonist naltriben coun teracted the stimulatory effects of both agonists with a potency about 10-fold higher than that of the selective delta(2) antagonist 7-benzy lidenenaltrexone. Moreover, pretreatment of olfactory bulb membranes w ith the nonequilibrium antagonist naltrindole 5'-isothiocyanate, which irreversibly blocks the delta(2) subtype, reduced the stimulatory eff ects of both DELT and DPDPE, whereas pretreatment with [D-Ala(2), Leu( 5), Cys(6)]enkephalin, which binds covalently to delta(1) receptors, f ailed to affect the response to the agonists. Similar results were obt ained in rat striatum. These data indicate that delta opioid receptors coupled to either stimulation or inhibition of adenylyl cyclase in tw o different brain areas predominantly belong to the delta(2) subtype.