Lack of antinociceptive cross-tolerance between [D-Pen2, D-Pen5]enkephalin and [D-Ala2]deltorphin ii in mice: Evidence for delta receptor subtypes

A. Mattia, Todd W Vanderah, H. I. Mosberg, Frank Porreca

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Abstract

This study has investigated the development of antinociceptive tolerance to, and cross-tolerance between, two highly selective delta agonists, [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Ala2] deltorphin II as well as to [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO), a highly selective mu agonist, in mice. Intracerebroventricular administration of DPDPE, [D-Ala2]deltorphin II and DAMGO each produced an antinociceptive effect. Pretreatment with i.c.v. DPDPE twice daily for 3 days resulted in tolerance to DPDPE as shown by a 4.8-fold rightward shift in the dose-response curve. In contrast, in DPDPE pretreated mice, the dose-response lines for [D-Ala2]deltorphin II and DAMGO were not altered when compared to those obtained in naive animals. The development of tolerance was also shown by pretreating mice with i.c.v. [D-Ala2]deltorphin II; following this pretreatment, the [D-Ala2Ideltorphin II dose-response line was displaced to the right by more than 37-fold. In contrast, in [D-Ala2]deltorphin II-pretreated mice, the dose-response lines for DPDPE and DAMGO were not altered compared to those obtained in naive animals. Finally, pretreatment with i.c.v. DAMGO produced a rightward displacement of the DAMGO dose-response line of 47-fold, indicating the development of antinociceptive tolerance. In DAMGO-pretreated mice, however, the dose-response lines for DPDPE and [D-Ala2]deltorphin II were not altered compared to those obtained in naive mice. Thus, the data indicate that antinociceptive tolerance develops to DPDPE, [D-Ala2]deltorphin II and DAMGO but that there is no cross-tolerance between these compounds. Although the lack of cross-tolerance between DAMGO and the two delta agonists is not surprising, the additional lack of cross-tolerance between DPDPE and [D-Ala2]deltorphin II suggests possible differences in their mechanism of action. As both DPDPE and [D-Ala2]deltorphin II are highly selective delta agonists which have been shown to elicit antinociception via interactions with a delta receptor, this lack of cross-tolerance suggests that these compounds produce antinociception via interaction with subtypes of delta receptors.

Original languageEnglish (US)
Pages (from-to)583-587
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume258
Issue number2
StatePublished - 1991

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D-Penicillamine (2,5)-Enkephalin
delta Opioid Receptor
Enkephalins
deltorphin
Ala(2)-deltorphin II

ASJC Scopus subject areas

  • Pharmacology

Cite this

@article{55097177c73c4b7f8df2992d014a886a,
title = "Lack of antinociceptive cross-tolerance between [D-Pen2, D-Pen5]enkephalin and [D-Ala2]deltorphin ii in mice: Evidence for delta receptor subtypes",
abstract = "This study has investigated the development of antinociceptive tolerance to, and cross-tolerance between, two highly selective delta agonists, [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Ala2] deltorphin II as well as to [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO), a highly selective mu agonist, in mice. Intracerebroventricular administration of DPDPE, [D-Ala2]deltorphin II and DAMGO each produced an antinociceptive effect. Pretreatment with i.c.v. DPDPE twice daily for 3 days resulted in tolerance to DPDPE as shown by a 4.8-fold rightward shift in the dose-response curve. In contrast, in DPDPE pretreated mice, the dose-response lines for [D-Ala2]deltorphin II and DAMGO were not altered when compared to those obtained in naive animals. The development of tolerance was also shown by pretreating mice with i.c.v. [D-Ala2]deltorphin II; following this pretreatment, the [D-Ala2Ideltorphin II dose-response line was displaced to the right by more than 37-fold. In contrast, in [D-Ala2]deltorphin II-pretreated mice, the dose-response lines for DPDPE and DAMGO were not altered compared to those obtained in naive animals. Finally, pretreatment with i.c.v. DAMGO produced a rightward displacement of the DAMGO dose-response line of 47-fold, indicating the development of antinociceptive tolerance. In DAMGO-pretreated mice, however, the dose-response lines for DPDPE and [D-Ala2]deltorphin II were not altered compared to those obtained in naive mice. Thus, the data indicate that antinociceptive tolerance develops to DPDPE, [D-Ala2]deltorphin II and DAMGO but that there is no cross-tolerance between these compounds. Although the lack of cross-tolerance between DAMGO and the two delta agonists is not surprising, the additional lack of cross-tolerance between DPDPE and [D-Ala2]deltorphin II suggests possible differences in their mechanism of action. As both DPDPE and [D-Ala2]deltorphin II are highly selective delta agonists which have been shown to elicit antinociception via interactions with a delta receptor, this lack of cross-tolerance suggests that these compounds produce antinociception via interaction with subtypes of delta receptors.",
author = "A. Mattia and Vanderah, {Todd W} and Mosberg, {H. I.} and Frank Porreca",
year = "1991",
language = "English (US)",
volume = "258",
pages = "583--587",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "2",

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TY - JOUR

T1 - Lack of antinociceptive cross-tolerance between [D-Pen2, D-Pen5]enkephalin and [D-Ala2]deltorphin ii in mice

T2 - Evidence for delta receptor subtypes

AU - Mattia, A.

AU - Vanderah, Todd W

AU - Mosberg, H. I.

AU - Porreca, Frank

PY - 1991

Y1 - 1991

N2 - This study has investigated the development of antinociceptive tolerance to, and cross-tolerance between, two highly selective delta agonists, [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Ala2] deltorphin II as well as to [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO), a highly selective mu agonist, in mice. Intracerebroventricular administration of DPDPE, [D-Ala2]deltorphin II and DAMGO each produced an antinociceptive effect. Pretreatment with i.c.v. DPDPE twice daily for 3 days resulted in tolerance to DPDPE as shown by a 4.8-fold rightward shift in the dose-response curve. In contrast, in DPDPE pretreated mice, the dose-response lines for [D-Ala2]deltorphin II and DAMGO were not altered when compared to those obtained in naive animals. The development of tolerance was also shown by pretreating mice with i.c.v. [D-Ala2]deltorphin II; following this pretreatment, the [D-Ala2Ideltorphin II dose-response line was displaced to the right by more than 37-fold. In contrast, in [D-Ala2]deltorphin II-pretreated mice, the dose-response lines for DPDPE and DAMGO were not altered compared to those obtained in naive animals. Finally, pretreatment with i.c.v. DAMGO produced a rightward displacement of the DAMGO dose-response line of 47-fold, indicating the development of antinociceptive tolerance. In DAMGO-pretreated mice, however, the dose-response lines for DPDPE and [D-Ala2]deltorphin II were not altered compared to those obtained in naive mice. Thus, the data indicate that antinociceptive tolerance develops to DPDPE, [D-Ala2]deltorphin II and DAMGO but that there is no cross-tolerance between these compounds. Although the lack of cross-tolerance between DAMGO and the two delta agonists is not surprising, the additional lack of cross-tolerance between DPDPE and [D-Ala2]deltorphin II suggests possible differences in their mechanism of action. As both DPDPE and [D-Ala2]deltorphin II are highly selective delta agonists which have been shown to elicit antinociception via interactions with a delta receptor, this lack of cross-tolerance suggests that these compounds produce antinociception via interaction with subtypes of delta receptors.

AB - This study has investigated the development of antinociceptive tolerance to, and cross-tolerance between, two highly selective delta agonists, [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Ala2] deltorphin II as well as to [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO), a highly selective mu agonist, in mice. Intracerebroventricular administration of DPDPE, [D-Ala2]deltorphin II and DAMGO each produced an antinociceptive effect. Pretreatment with i.c.v. DPDPE twice daily for 3 days resulted in tolerance to DPDPE as shown by a 4.8-fold rightward shift in the dose-response curve. In contrast, in DPDPE pretreated mice, the dose-response lines for [D-Ala2]deltorphin II and DAMGO were not altered when compared to those obtained in naive animals. The development of tolerance was also shown by pretreating mice with i.c.v. [D-Ala2]deltorphin II; following this pretreatment, the [D-Ala2Ideltorphin II dose-response line was displaced to the right by more than 37-fold. In contrast, in [D-Ala2]deltorphin II-pretreated mice, the dose-response lines for DPDPE and DAMGO were not altered compared to those obtained in naive animals. Finally, pretreatment with i.c.v. DAMGO produced a rightward displacement of the DAMGO dose-response line of 47-fold, indicating the development of antinociceptive tolerance. In DAMGO-pretreated mice, however, the dose-response lines for DPDPE and [D-Ala2]deltorphin II were not altered compared to those obtained in naive mice. Thus, the data indicate that antinociceptive tolerance develops to DPDPE, [D-Ala2]deltorphin II and DAMGO but that there is no cross-tolerance between these compounds. Although the lack of cross-tolerance between DAMGO and the two delta agonists is not surprising, the additional lack of cross-tolerance between DPDPE and [D-Ala2]deltorphin II suggests possible differences in their mechanism of action. As both DPDPE and [D-Ala2]deltorphin II are highly selective delta agonists which have been shown to elicit antinociception via interactions with a delta receptor, this lack of cross-tolerance suggests that these compounds produce antinociception via interaction with subtypes of delta receptors.

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