Evidence for a single functional opioid delta receptor subtype in the mouse isolated vas deferens

K. D. Wild, V. J. Carlisi, H. I. Mosberg, W. D. Bowen, P. S. Portoghese, M. Sultana, A. E. Takemori, Victor J Hruby, Frank Porreca

Research output: Contribution to journalArticle

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Abstract

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 languageEnglish (US)
Pages (from-to)831-838
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume264
Issue number2
StatePublished - 1993

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D-Penicillamine (2,5)-Enkephalin
delta Opioid Receptor
Vas Deferens
Enkephalins
Opioid Receptors
Naloxone
deltorphin

ASJC Scopus subject areas

  • Pharmacology

Cite this

Wild, K. D., Carlisi, V. J., Mosberg, H. I., Bowen, W. D., Portoghese, P. S., Sultana, M., ... Porreca, F. (1993). Evidence for a single functional opioid delta receptor subtype in the mouse isolated vas deferens. Journal of Pharmacology and Experimental Therapeutics, 264(2), 831-838.

Evidence for a single functional opioid delta receptor subtype in the mouse isolated vas deferens. / Wild, K. D.; Carlisi, V. J.; Mosberg, H. I.; Bowen, W. D.; Portoghese, P. S.; Sultana, M.; Takemori, A. E.; Hruby, Victor J; Porreca, Frank.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 264, No. 2, 1993, p. 831-838.

Research output: Contribution to journalArticle

Wild, KD, Carlisi, VJ, Mosberg, HI, Bowen, WD, Portoghese, PS, Sultana, M, Takemori, AE, Hruby, VJ & Porreca, F 1993, 'Evidence for a single functional opioid delta receptor subtype in the mouse isolated vas deferens', Journal of Pharmacology and Experimental Therapeutics, vol. 264, no. 2, pp. 831-838.
Wild, K. D. ; Carlisi, V. J. ; Mosberg, H. I. ; Bowen, W. D. ; Portoghese, P. S. ; Sultana, M. ; Takemori, A. E. ; Hruby, Victor J ; Porreca, Frank. / Evidence for a single functional opioid delta receptor subtype in the mouse isolated vas deferens. In: Journal of Pharmacology and Experimental Therapeutics. 1993 ; Vol. 264, No. 2. pp. 831-838.
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AU - Carlisi, V. J.

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AU - Portoghese, P. S.

AU - Sultana, M.

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N2 - 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.

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