Tags

Type your tag names separated by a space and hit enter

Antisense oligodeoxynucleotide to the CCKB receptor produces naltrindole- and [Leu5]enkephalin antiserum-sensitive enhancement of morphine antinociception.
Neuroreport. 1994 Dec 20; 5(18):2601-5.N

Abstract

Cholecystokinin (CCK) has been shown to attenuate, while CCK antagonists enhance, the antinociceptive activity of morphine, suggesting that this peptide may act as an endogenous modulator of the opioid system. Here, we have investigated the effects of administration of a synthetic oligodeoxynucleotide (oligo) complementary to the 5' coding region of the cloned mouse CCKB receptor (antisense), or a mismatch oligo, on the antinociceptive effects of morphine. Intracerebroventricular (i.c.v.) treatment of mice with CCKB antisense, but not mismatch, oligo for 3 days resulted in an enhancement of the antinociceptive potency of i.c.v. morphine, as indicated by an approximately 6-fold leftward shift of the dose-effect curve. The antinociceptive effects of morphine in control and CCKB antisense-treated animals were investigated in the presence or absence of naltrindole, an opioid delta receptor antagonist, as well as in the presence or absence of antisera directed against either [Leu5]- or [Met5]enkephalin. The enhanced potency of morphine in mice pretreated with CCKB antisense oligo was blocked by a delta-selective dose of naltrindole and antisera to [Leu5]enkephalin, but not [Met5]enkephalin; naltrindole, or antisera towards [Leu5]enkephalin or [Met5]enkephalin did not produce antinociceptive effects when given alone and did not alter the antinociceptive actions of morphine in control mice. These data suggest that CCK may act via CCKB receptors to tonically inhibit the release of [Leu5]enkephalin, or a [Leu5]enkephalin-like peptide. The enhancement of morphine antinociception seen in the presence of blockade of the CCKB receptor may be the result of the well-known enhancement of morphine antinociception by opioid delta agonists.

Authors+Show Affiliations

Department of Pharmacology, University of Arizona Health Science Center, Tucson 85724.No 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

7696612

Citation

Vanderah, T W., et al. "Antisense Oligodeoxynucleotide to the CCKB Receptor Produces Naltrindole- and [Leu5]enkephalin Antiserum-sensitive Enhancement of Morphine Antinociception." Neuroreport, vol. 5, no. 18, 1994, pp. 2601-5.
Vanderah TW, Lai J, Yamamura HI, et al. Antisense oligodeoxynucleotide to the CCKB receptor produces naltrindole- and [Leu5]enkephalin antiserum-sensitive enhancement of morphine antinociception. Neuroreport. 1994;5(18):2601-5.
Vanderah, T. W., Lai, J., Yamamura, H. I., & Porreca, F. (1994). Antisense oligodeoxynucleotide to the CCKB receptor produces naltrindole- and [Leu5]enkephalin antiserum-sensitive enhancement of morphine antinociception. Neuroreport, 5(18), 2601-5.
Vanderah TW, et al. Antisense Oligodeoxynucleotide to the CCKB Receptor Produces Naltrindole- and [Leu5]enkephalin Antiserum-sensitive Enhancement of Morphine Antinociception. Neuroreport. 1994 Dec 20;5(18):2601-5. PubMed PMID: 7696612.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antisense oligodeoxynucleotide to the CCKB receptor produces naltrindole- and [Leu5]enkephalin antiserum-sensitive enhancement of morphine antinociception. AU - Vanderah,T W, AU - Lai,J, AU - Yamamura,H I, AU - Porreca,F, PY - 1994/12/20/pubmed PY - 1994/12/20/medline PY - 1994/12/20/entrez SP - 2601 EP - 5 JF - Neuroreport JO - Neuroreport VL - 5 IS - 18 N2 - Cholecystokinin (CCK) has been shown to attenuate, while CCK antagonists enhance, the antinociceptive activity of morphine, suggesting that this peptide may act as an endogenous modulator of the opioid system. Here, we have investigated the effects of administration of a synthetic oligodeoxynucleotide (oligo) complementary to the 5' coding region of the cloned mouse CCKB receptor (antisense), or a mismatch oligo, on the antinociceptive effects of morphine. Intracerebroventricular (i.c.v.) treatment of mice with CCKB antisense, but not mismatch, oligo for 3 days resulted in an enhancement of the antinociceptive potency of i.c.v. morphine, as indicated by an approximately 6-fold leftward shift of the dose-effect curve. The antinociceptive effects of morphine in control and CCKB antisense-treated animals were investigated in the presence or absence of naltrindole, an opioid delta receptor antagonist, as well as in the presence or absence of antisera directed against either [Leu5]- or [Met5]enkephalin. The enhanced potency of morphine in mice pretreated with CCKB antisense oligo was blocked by a delta-selective dose of naltrindole and antisera to [Leu5]enkephalin, but not [Met5]enkephalin; naltrindole, or antisera towards [Leu5]enkephalin or [Met5]enkephalin did not produce antinociceptive effects when given alone and did not alter the antinociceptive actions of morphine in control mice. These data suggest that CCK may act via CCKB receptors to tonically inhibit the release of [Leu5]enkephalin, or a [Leu5]enkephalin-like peptide. The enhancement of morphine antinociception seen in the presence of blockade of the CCKB receptor may be the result of the well-known enhancement of morphine antinociception by opioid delta agonists. SN - 0959-4965 UR - https://www.unboundmedicine.com/medline/citation/7696612/Antisense_oligodeoxynucleotide_to_the_CCKB_receptor_produces_naltrindole__and_[Leu5]enkephalin_antiserum_sensitive_enhancement_of_morphine_antinociception_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=7696612.ui DB - PRIME DP - Unbound Medicine ER -