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Enhancement of morphine antinociception by a CCKB antagonist in mice is mediated via opioid delta receptors.
J Pharmacol Exp Ther. 1996 Jul; 278(1):212-9.JP

Abstract

This study investigated the possible involvement of opioid delta receptors in the modulation of morphine antinociceptive potency produced by L365,260 a CCKB antagonist. Intracerebroventricular (i.c.v.), intratheoal (i.th.) or subcutaneous (s.c.) L365,260 alone did not produce any antinociceptive actions in the mouse warm-water tail-nick test. Treatment with L365,260 by any of these routes produced a leftward shift of the corresponding morphine dose-effect curve that was blocked by pretreatment with a receptor selective dose of s.c. naltrindole, an opioid delta receptor antagonist. Pretreatment with i.c.v. antisera to [Leu5]enkephalin also blocked the leftward displacement of the i.c.v. morphine dose-effect curve resulting from L365,260 but did not directly alter the i.c.v. morphine dose-effect curve; antisera to [Met5]enkephalin did not alter the effects of morphine or the modulation of morphine antinociception produced by L365,260. Repeated pretreatment with L365,260 resulted in a progressive decrease in the magnitude of the morphine modulatory action (i.e., L365,260 "tolerance"). In these "L365,260-tolerant" mice, the dose-effect curve for i.c.v. [D-Ala2, Glu4]deltrophin (a selective delta agonist) was displaced to the right by approximately 8.2-fold. The i.c.v. administration of [Leu5]enkephalin produced a leftward displacement of the i.c.v. morphine dose-effect curve that diminished after repeated administration (i.e., [Leu5]enkephalin "tolerance"). In "[Leu5]enkephalin-tolerant" mice, L365,260 failed to produce the leftward shift of the morphine dose-effect curve seen in control animals. That is, two-way antinociceptive cross-tolerance was observed between an opioid delta agonist and a CCKB receptor antagonist. Intracerebroventricular thiorphan, a peptidase inhibitor, did not elicit antinociception directly. Co-administration of thiorphan with L365,260 elicited significant antinociception that was blocked by naltrindole or antisera to [Leu5]enkephalin; antisera to [Met5]enkephalin had no effect. Repeated administration of i.c.v. [D-Ala2, Glu4]deltorphin resulted in a progressively decreasing antinociceptive effect (i.e., [D-Ala2, Glu4]deltorphin "tolerance"). In "[D-Ala2, Glu4]deltorphin-tolerant" mice, the thiorphan/L365,260 antinociceptive effect was inhibited. Collectively, these data suggest that CCK interacts at the CCKB receptor to inhibit tonically the release and/or availability of an endogenous substance acting at opioid delta receptors. The subsequent enhancement of morphine antinociceptive potency may reflect the well-known modulation of morphine antinociception produced by opioid delta receptor agonists. In this case, the latter may be [Leu5]enkephalin or a [Leu5]enkephalin-like substance.

Authors+Show Affiliations

Department of Pharmacology, University of Arizona Health Science Center, Tucson, USA.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

8764354

Citation

Vanderah, T W., et al. "Enhancement of Morphine Antinociception By a CCKB Antagonist in Mice Is Mediated Via Opioid Delta Receptors." The Journal of Pharmacology and Experimental Therapeutics, vol. 278, no. 1, 1996, pp. 212-9.
Vanderah TW, Bernstein RN, Yamamura HI, et al. Enhancement of morphine antinociception by a CCKB antagonist in mice is mediated via opioid delta receptors. J Pharmacol Exp Ther. 1996;278(1):212-9.
Vanderah, T. W., Bernstein, R. N., Yamamura, H. I., Hruby, V. J., & Porreca, F. (1996). Enhancement of morphine antinociception by a CCKB antagonist in mice is mediated via opioid delta receptors. The Journal of Pharmacology and Experimental Therapeutics, 278(1), 212-9.
Vanderah TW, et al. Enhancement of Morphine Antinociception By a CCKB Antagonist in Mice Is Mediated Via Opioid Delta Receptors. J Pharmacol Exp Ther. 1996;278(1):212-9. PubMed PMID: 8764354.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhancement of morphine antinociception by a CCKB antagonist in mice is mediated via opioid delta receptors. AU - Vanderah,T W, AU - Bernstein,R N, AU - Yamamura,H I, AU - Hruby,V J, AU - Porreca,F, PY - 1996/7/1/pubmed PY - 1996/7/1/medline PY - 1996/7/1/entrez SP - 212 EP - 9 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 278 IS - 1 N2 - This study investigated the possible involvement of opioid delta receptors in the modulation of morphine antinociceptive potency produced by L365,260 a CCKB antagonist. Intracerebroventricular (i.c.v.), intratheoal (i.th.) or subcutaneous (s.c.) L365,260 alone did not produce any antinociceptive actions in the mouse warm-water tail-nick test. Treatment with L365,260 by any of these routes produced a leftward shift of the corresponding morphine dose-effect curve that was blocked by pretreatment with a receptor selective dose of s.c. naltrindole, an opioid delta receptor antagonist. Pretreatment with i.c.v. antisera to [Leu5]enkephalin also blocked the leftward displacement of the i.c.v. morphine dose-effect curve resulting from L365,260 but did not directly alter the i.c.v. morphine dose-effect curve; antisera to [Met5]enkephalin did not alter the effects of morphine or the modulation of morphine antinociception produced by L365,260. Repeated pretreatment with L365,260 resulted in a progressive decrease in the magnitude of the morphine modulatory action (i.e., L365,260 "tolerance"). In these "L365,260-tolerant" mice, the dose-effect curve for i.c.v. [D-Ala2, Glu4]deltrophin (a selective delta agonist) was displaced to the right by approximately 8.2-fold. The i.c.v. administration of [Leu5]enkephalin produced a leftward displacement of the i.c.v. morphine dose-effect curve that diminished after repeated administration (i.e., [Leu5]enkephalin "tolerance"). In "[Leu5]enkephalin-tolerant" mice, L365,260 failed to produce the leftward shift of the morphine dose-effect curve seen in control animals. That is, two-way antinociceptive cross-tolerance was observed between an opioid delta agonist and a CCKB receptor antagonist. Intracerebroventricular thiorphan, a peptidase inhibitor, did not elicit antinociception directly. Co-administration of thiorphan with L365,260 elicited significant antinociception that was blocked by naltrindole or antisera to [Leu5]enkephalin; antisera to [Met5]enkephalin had no effect. Repeated administration of i.c.v. [D-Ala2, Glu4]deltorphin resulted in a progressively decreasing antinociceptive effect (i.e., [D-Ala2, Glu4]deltorphin "tolerance"). In "[D-Ala2, Glu4]deltorphin-tolerant" mice, the thiorphan/L365,260 antinociceptive effect was inhibited. Collectively, these data suggest that CCK interacts at the CCKB receptor to inhibit tonically the release and/or availability of an endogenous substance acting at opioid delta receptors. The subsequent enhancement of morphine antinociceptive potency may reflect the well-known modulation of morphine antinociception produced by opioid delta receptor agonists. In this case, the latter may be [Leu5]enkephalin or a [Leu5]enkephalin-like substance. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8764354/Enhancement_of_morphine_antinociception_by_a_CCKB_antagonist_in_mice_is_mediated_via_opioid_delta_receptors_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8764354 DB - PRIME DP - Unbound Medicine ER -