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Opioid agonist and antagonist antinociceptive properties of [D-Ala2,Leu5,Cys6]enkephalin: selective actions at the deltanoncomplexed site.
J Pharmacol Exp Ther. 1990 Nov; 255(2):636-41.JP

Abstract

The present study used the irreversibly binding enkephalin analog, [D-Ala2,Leu5,Cys6]enkephalin (DALCE) in an effort to determine whether selective agonist and antagonist properties could be demonstrated at hypothesized types of opioid delta receptors previously termed the deltanoncomplexed and the deltacomplexed sites. These putative subtypes of delta receptors have been functionally distinguished on the basis of involvement (i.e., deltacomplexed) in the modulation of mu-mediated effects such as antinociception. Intracerebroventricular administration of DALCE or the reference delta and mu agonists, [D-Pen2,D-Pen5]enkephalin (DPDPE) and morphine, to mice all produced antinociception in the warm-water tail-flick test in a dose- and time-related manner. Maximal effects with DALCE were seen at +10 min and significant antinociception could be detected for approximately 1 hr; DALCE was 3- and 90-fold more potent than i.c.v. morphine and DPDPE, respectively. The antinociceptive effects of i.c.v. DALCE and DPDPE, but not those of morphine, were antagonized by the selective delta antagonist, N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH, suggesting that the antinociception associated with the peptides was mediated through a delta receptor. DALCE pretreatment up to 24 hr before testing, a time at which this compound did not produce antinociception, significantly blocked the i.c.v. DPDPE antinociceptive effect as well as that of DALCE itself, but not that of morphine, suggesting long-lasting DALCE antagonism at a delta receptor. Modulation of morphine antinociception was demonstrated with subeffective doses of i.c.v. DPDPE or [Met5]enkephalin, but not with subeffective doses of i.c.v. DALCE.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Department of Pharmacology, University of Arizona Health Sciences Center, Tucson.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2173752

Citation

Qi, J A., et al. "Opioid Agonist and Antagonist Antinociceptive Properties of [D-Ala2,Leu5,Cys6]enkephalin: Selective Actions at the Deltanoncomplexed Site." The Journal of Pharmacology and Experimental Therapeutics, vol. 255, no. 2, 1990, pp. 636-41.
Qi JA, Bowen WD, Mosberg HI, et al. Opioid agonist and antagonist antinociceptive properties of [D-Ala2,Leu5,Cys6]enkephalin: selective actions at the deltanoncomplexed site. J Pharmacol Exp Ther. 1990;255(2):636-41.
Qi, J. A., Bowen, W. D., Mosberg, H. I., Rothman, R. B., & Porreca, F. (1990). Opioid agonist and antagonist antinociceptive properties of [D-Ala2,Leu5,Cys6]enkephalin: selective actions at the deltanoncomplexed site. The Journal of Pharmacology and Experimental Therapeutics, 255(2), 636-41.
Qi JA, et al. Opioid Agonist and Antagonist Antinociceptive Properties of [D-Ala2,Leu5,Cys6]enkephalin: Selective Actions at the Deltanoncomplexed Site. J Pharmacol Exp Ther. 1990;255(2):636-41. PubMed PMID: 2173752.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Opioid agonist and antagonist antinociceptive properties of [D-Ala2,Leu5,Cys6]enkephalin: selective actions at the deltanoncomplexed site. AU - Qi,J A, AU - Bowen,W D, AU - Mosberg,H I, AU - Rothman,R B, AU - Porreca,F, PY - 1990/11/1/pubmed PY - 1990/11/1/medline PY - 1990/11/1/entrez SP - 636 EP - 41 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 255 IS - 2 N2 - The present study used the irreversibly binding enkephalin analog, [D-Ala2,Leu5,Cys6]enkephalin (DALCE) in an effort to determine whether selective agonist and antagonist properties could be demonstrated at hypothesized types of opioid delta receptors previously termed the deltanoncomplexed and the deltacomplexed sites. These putative subtypes of delta receptors have been functionally distinguished on the basis of involvement (i.e., deltacomplexed) in the modulation of mu-mediated effects such as antinociception. Intracerebroventricular administration of DALCE or the reference delta and mu agonists, [D-Pen2,D-Pen5]enkephalin (DPDPE) and morphine, to mice all produced antinociception in the warm-water tail-flick test in a dose- and time-related manner. Maximal effects with DALCE were seen at +10 min and significant antinociception could be detected for approximately 1 hr; DALCE was 3- and 90-fold more potent than i.c.v. morphine and DPDPE, respectively. The antinociceptive effects of i.c.v. DALCE and DPDPE, but not those of morphine, were antagonized by the selective delta antagonist, N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH, suggesting that the antinociception associated with the peptides was mediated through a delta receptor. DALCE pretreatment up to 24 hr before testing, a time at which this compound did not produce antinociception, significantly blocked the i.c.v. DPDPE antinociceptive effect as well as that of DALCE itself, but not that of morphine, suggesting long-lasting DALCE antagonism at a delta receptor. Modulation of morphine antinociception was demonstrated with subeffective doses of i.c.v. DPDPE or [Met5]enkephalin, but not with subeffective doses of i.c.v. DALCE.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/2173752/Opioid_agonist_and_antagonist_antinociceptive_properties_of_[D_Ala2Leu5Cys6]enkephalin:_selective_actions_at_the_deltanoncomplexed_site_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=2173752 DB - PRIME DP - Unbound Medicine ER -