PMID- 7696612
OWN - NLM
STAT- MEDLINE
DCOM- 19950504
LR  - 20190718
IS  - 0959-4965 (Print)
IS  - 0959-4965 (Linking)
VI  - 5
IP  - 18
DP  - 1994 Dec 20
TI  - Antisense oligodeoxynucleotide to the CCKB receptor produces naltrindole- and 
      [Leu5]enkephalin antiserum-sensitive enhancement of morphine antinociception.
PG  - 2601-5
AB  - 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.
FAU - Vanderah, T W
AU  - Vanderah TW
AD  - Department of Pharmacology, University of Arizona Health Science Center, Tucson 
      85724.
FAU - Lai, J
AU  - Lai J
FAU - Yamamura, H I
AU  - Yamamura HI
FAU - Porreca, F
AU  - Porreca F
LA  - eng
GR  - DA 00185/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Neuroreport
JT  - Neuroreport
JID - 9100935
RN  - 0 (Immune Sera)
RN  - 0 (Narcotic Antagonists)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Receptors, Cholecystokinin)
RN  - 58822-25-6 (Enkephalin, Leucine)
RN  - 5S6W795CQM (Naltrexone)
RN  - 76I7G6D29C (Morphine)
RN  - G167Z38QA4 (naltrindole)
SB  - IM
MH  - Animals
MH  - Drug Synergism
MH  - Enkephalin, Leucine/immunology/*physiology
MH  - Immune Sera/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Morphine/*pharmacology
MH  - Naltrexone/*analogs & derivatives/pharmacology
MH  - Narcotic Antagonists/pharmacology
MH  - Nociceptors/*drug effects
MH  - Oligonucleotides, Antisense/*pharmacology
MH  - Receptors, Cholecystokinin/*genetics
EDAT- 1994/12/20 00:00
MHDA- 1994/12/20 00:01
CRDT- 1994/12/20 00:00
PHST- 1994/12/20 00:00 [pubmed]
PHST- 1994/12/20 00:01 [medline]
PHST- 1994/12/20 00:00 [entrez]
AID - 10.1097/00001756-199412000-00049 [doi]
PST - ppublish
SO  - Neuroreport. 1994 Dec 20;5(18):2601-5. doi: 10.1097/00001756-199412000-00049.