The identification of opioid δ receptor subtypes in mouse brain led to the investigation of the nature of the opioid δ receptors in the mouse isolated vas deferens in vitro. Noncumulative concentration-effect curves were constructed for DPDPE (δ1 agonist) and [D-Ala2, Glu4]deltorphin (δ2 agonist) in control tissues, or in tissues which had been incubated with either [D-Ala2, Leu5, Cys6] enkephalin (DALCE) (noncompetitive δ1 antagonist) or 5'-naltrindole isothiocyanate (5'-NTII) (noncompetitive δ2 antagonist). Incubation of the tissues with DALCE, under either oxygenated or nonoxygenated conditions, did not alter the concentration-effect curves for either agonist. In contrast, incubation of the tissues with 5'-NTII resulted in a significant rightward displacement of the concentration-effect curves of both DPDPE and [D-Ala2, Glu4]deltorphin. Additionally, naltriben, a selective and competitive δ2 antagonist, showed no significant difference in its ability to antagonize a fixed, submaximal concentration of either DPDPE or [D-Ala2, Glu4]deltorphin. Furthermore, there was no significant difference in the affinity of naloxone (i.e., pA2) at the receptor(s) acted upon by either DPDPE or [D-Ala2, Glu4]deltorphin. Tolerance to DPDPE or [D- Ala2, Glu4]deltorphin was produced by incubation of the tissues with these agonists; construction of the [D-Ala2, Glu4]deltorphin concentration- effect curve in DPDPE-tolerant tissues demonstrated cross-tolerance between these agonists and, conversely, construction of DPDPE concentration-effect curves in [D-Ala2, Glu4]deltorphin-tolerant tissues revealed cross- tolerance between these agonists. Thus, the present data provide support for one subtype of opioid δ receptor in the mouse isolated vas deferens based on 1) the lack of antagonism of the effects of both agonists selective for δ1 and δ2 receptor subtypes by DALCE, a δ1 antagonist, 2) the antagonism of δ1 and δ2 agonists by 5'-NTII or naltriben (δ2 antagonists), 3) the similar antagonist potency of NTB against either DPDPE or [D-Ala2, Glu4]deltorphin, 4) the lack of significant difference in the naloxone pA2 against either δ agonist and 5) the demonstration of two-way cross-tolerance between the effects of DPDPE and [D-Ala2, Glu4]deltorphin in this tissue.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Dec 1 1993|