PMID- 12015208
OWN - NLM
STAT- MEDLINE
DCOM- 20020925
LR  - 20191210
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 42
IP  - 6
DP  - 2002 May
TI  - Glycosylated phosducin-like protein long regulates opioid receptor function in 
      mouse brain.
PG  - 813-28
AB  - Phosducin (Phd), a protein that in retina regulates rhodopsin desensitization by 
      controlling the activity of Gt beta gamma-dependent G-protein-coupled receptor 
      kinases (GRKs), is present in very low levels in the CNS of mammals. However, 
      this tissue contains proteins of related sequence and function. This paper 
      reports the presence of N-glycosylated phosducin-like protein long (PhLP(L)) in 
      all structures of mouse CNS, mainly in synaptic plasma membranes and associated 
      with G beta subunits and 14-3-3 proteins. To analyze the role PhLP(L) in opioid 
      receptor desensitization, its expression was reduced by the use of antisense 
      oligodeoxynucleotides (ODNs). The antinociception induced by morphine, [D-Ala(2), 
      N-MePhe(4),Gly-ol(5)]-enkephalin (DAMGO), beta-endorphin, [D-Ala(2)]deltorphin 
      II, [D-Pen(2,5)]-enkephalin (DPDPE) or clonidine in the tail-flick test was 
      reduced in PhLP(L)-knock-down mice. A single intracerebroventricular (icv)-ED(80) 
      analgesic dose of morphine gave rise to acute tolerance that lasted for 4 days, 
      but which was prevented or reversed by icv-injection of myristoylated (myr(+)) 
      G(i2)alpha subunits. PhLP(L) knock-down brought about a myr(+)-G(i2)alpha 
      subunit-insensitive acute tolerance to morphine that was still present after 8 
      days. It also diminished the specific binding of 
      (125)I-Tyr(27)-beta-endorphin-(1-31) (human) to mouse periaqueductal gray matter 
      membranes. After being exposed to chronic morphine treatment, post-dependent mice 
      required about 10 days for complete recovery of morphine antinociception. The 
      impairment of PhLP(L) extended this period beyond 17 days. It is concluded that 
      PhLP(L) knock-down facilitates desensitization and uncoupling of opioid 
      receptors.
FAU - Garzon, J
AU  - Garzon J
AD  - Neurofarmacologia, Instituto Cajal, Consejo Superior de Investigaciones 
      Cientificas, Avd Doctor Arce, 37, E-28002 Madrid, Spain. jgarzon@cajal.csic.es
FAU - Rodriguez-Diaz, M
AU  - Rodriguez-Diaz M
FAU - Lopez-Fando, A
AU  - Lopez-Fando A
FAU - Garcia-Espana, A
AU  - Garcia-Espana A
FAU - Sanchez-Blazquez, P
AU  - Sanchez-Blazquez P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Carrier Proteins)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (PDCL protein, human)
RN  - 0 (Pdcl protein, mouse)
RN  - 0 (Pdcl protein, rat)
RN  - 0 (Receptors, Opioid)
RN  - 36B82AMQ7N (Naloxone)
RN  - 76I7G6D29C (Morphine)
SB  - IM
MH  - Analgesics, Opioid/pharmacology
MH  - Animals
MH  - Brain/drug effects/*metabolism
MH  - Carrier Proteins/biosynthesis/genetics/*physiology
MH  - Dose-Response Relationship, Drug
MH  - Drug Tolerance
MH  - Glycosylation
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Molecular Chaperones
MH  - Morphine/adverse effects/pharmacology
MH  - Naloxone/pharmacology
MH  - Nerve Tissue Proteins/biosynthesis/deficiency/genetics/*physiology
MH  - Rats
MH  - Receptors, Opioid/agonists/*physiology
MH  - Retina/drug effects/metabolism
MH  - Substance Withdrawal Syndrome/genetics/metabolism
EDAT- 2002/05/17 10:00
MHDA- 2002/09/26 06:00
CRDT- 2002/05/17 10:00
PHST- 2002/05/17 10:00 [pubmed]
PHST- 2002/09/26 06:00 [medline]
PHST- 2002/05/17 10:00 [entrez]
AID - S0028390802000278 [pii]
AID - 10.1016/s0028-3908(02)00027-8 [doi]
PST - ppublish
SO  - Neuropharmacology. 2002 May;42(6):813-28. doi: 10.1016/s0028-3908(02)00027-8.