PMID- 8764354
OWN - NLM
STAT- MEDLINE
DCOM- 19960923
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 278
IP  - 1
DP  - 1996 Jul
TI  - Enhancement of morphine antinociception by a CCKB antagonist in mice is mediated 
      via opioid delta receptors.
PG  - 212-9
AB  - 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.
FAU - Vanderah, T W
AU  - Vanderah TW
AD  - Department of Pharmacology, University of Arizona Health Science Center, Tucson, 
      USA.
FAU - Bernstein, R N
AU  - Bernstein RN
FAU - Yamamura, H I
AU  - Yamamura HI
FAU - Hruby, V J
AU  - Hruby VJ
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  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Oligopeptides)
RN  - 0 (Receptors, Cholecystokinin)
RN  - 0 (Receptors, Opioid, delta)
RN  - 119975-64-3 (deltorphin)
RN  - 76I7G6D29C (Morphine)
SB  - IM
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Morphine/*pharmacology
MH  - Oligopeptides/pharmacology
MH  - Pain Measurement
MH  - Receptors, Cholecystokinin/*antagonists & inhibitors
MH  - Receptors, Opioid, delta/*drug effects
EDAT- 1996/07/01 00:00
MHDA- 1996/07/01 00:01
CRDT- 1996/07/01 00:00
PHST- 1996/07/01 00:00 [pubmed]
PHST- 1996/07/01 00:01 [medline]
PHST- 1996/07/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1996 Jul;278(1):212-9.