Mc. Olianas et P. Onali, PARTICIPATION OF DELTA-OPIOID RECEPTOR SUBTYPES IN THE STIMULATION OFADENYLYL-CYCLASE ACTIVITY IN RAT OLFACTORY-BULB, The Journal of pharmacology and experimental therapeutics, 275(3), 1995, pp. 1560-1567
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.