PMID- 24350273
OWN - NLM
STAT- MEDLINE
DCOM- 20140811
LR  - 20211021
IS  - 2314-6141 (Electronic)
IS  - 2314-6133 (Print)
VI  - 2013
DP  - 2013
TI  - Ligand-specific regulation of the endogenous mu-opioid receptor by chronic 
      treatment with mu-opioid peptide agonists.
PG  - 501086
LID - 10.1155/2013/501086 [doi]
LID - 501086
AB  - Since the discovery of the endomorphins (EM), the postulated endogenous peptide 
      agonists of the mu-opioid receptors, several analogues have been synthesized to 
      improve their binding and pharmacological profiles. We have shown previously that 
      a new analogue, cis-1S,2R-aminocyclohexanecarboxylic acid(2)-endomorphin-2 
      (ACHC-EM2), had elevated mu-receptor affinity, selectivity, and proteolytic 
      stability over the parent compound. In the present work, we have studied its 
      antinociceptive effects and receptor regulatory processes. ACHC-EM2 displayed a 
      somewhat higher (60%) acute antinociceptive response than the parent peptide, EM2 
      (45%), which peaked at 10 min after intracerebroventricular (icv) administration 
      in the rat tail-flick test. Analgesic tolerance developed to the antinociceptive 
      effect of ACHC-EM2 upon its repeated icv injection that was complete by a 10-day 
      treatment. This was accompanied by attenuated coupling of mu-sites to G-proteins 
      in subcellular fractions of rat brain. Also, the density of mu-receptors was 
      upregulated by about 40% in the light membrane fraction, with no detectable 
      changes in surface binding. Distinct receptor regulatory processes were noted in 
      subcellular fractions of rat brains made tolerant by the prototypic full 
      mu-agonist peptide, DAMGO, and its chloromethyl ketone derivative, DAMCK. These 
      results are discussed in light of the recently discovered phenomenon, that is, 
      the "so-called biased agonism" or "functional selectivity".
FAU - Muranyi, Marianna
AU  - Muranyi M
AD  - Institute of Biochemistry, Biological Research Center, Hungarian Academy of 
      Sciences, P.O. Box 521, Szeged 6701, Hungary.
FAU - Cinar, Resat
AU  - Cinar R
AD  - Institute of Biochemistry, Biological Research Center, Hungarian Academy of 
      Sciences, P.O. Box 521, Szeged 6701, Hungary.
FAU - Kekesi, Orsolya
AU  - Kekesi O
AD  - Institute of Biochemistry, Biological Research Center, Hungarian Academy of 
      Sciences, P.O. Box 521, Szeged 6701, Hungary.
FAU - Birkas, Erika
AU  - Birkas E
AD  - Institute of Biochemistry, Biological Research Center, Hungarian Academy of 
      Sciences, P.O. Box 521, Szeged 6701, Hungary.
FAU - Fabian, Gabriella
AU  - Fabian G
AD  - Institute of Biochemistry, Biological Research Center, Hungarian Academy of 
      Sciences, P.O. Box 521, Szeged 6701, Hungary.
FAU - Bozo, Beata
AU  - Bozo B
AD  - Institute of Biochemistry, Biological Research Center, Hungarian Academy of 
      Sciences, P.O. Box 521, Szeged 6701, Hungary.
FAU - Zentai, Andras
AU  - Zentai A
AD  - Institute of Biochemistry, Biological Research Center, Hungarian Academy of 
      Sciences, P.O. Box 521, Szeged 6701, Hungary ; Department of Pathophysiology, 
      Faculty of Medicine, University of Szeged, Szeged, Hungary.
FAU - Toth, Geza
AU  - Toth G
AD  - Institute of Biochemistry, Biological Research Center, Hungarian Academy of 
      Sciences, P.O. Box 521, Szeged 6701, Hungary.
FAU - Kicsi, Emese Gabriella
AU  - Kicsi EG
AD  - Institute of Biochemistry, Biological Research Center, Hungarian Academy of 
      Sciences, P.O. Box 521, Szeged 6701, Hungary.
FAU - Macsai, Monika
AU  - Macsai M
AD  - Department of Pathophysiology, Faculty of Medicine, University of Szeged, Szeged, 
      Hungary.
FAU - Dochnal, Roberta
AU  - Dochnal R
AD  - Department of Pathophysiology, Faculty of Medicine, University of Szeged, Szeged, 
      Hungary.
FAU - Szabo, Gyula
AU  - Szabo G
AD  - Department of Pathophysiology, Faculty of Medicine, University of Szeged, Szeged, 
      Hungary.
FAU - Szucs, Maria
AU  - Szucs M
AD  - Institute of Biochemistry, Biological Research Center, Hungarian Academy of 
      Sciences, P.O. Box 521, Szeged 6701, Hungary.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131124
PL  - United States
TA  - Biomed Res Int
JT  - BioMed research international
JID - 101600173
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (Analgesics)
RN  - 0 (Ligands)
RN  - 0 (Opioid Peptides)
RN  - 0 (Receptors, Opioid, mu)
RN  - 100929-53-1 (Enkephalin, Ala(2)-MePhe(4)-Gly(5)-)
RN  - 109377-04-0 (tyrosyl-alanyl-glycyl-N(alpha)-methylphenylalanine chloromethyl 
      ketone)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Amino Acid Chloromethyl Ketones/pharmacology
MH  - Analgesics/*pharmacology
MH  - Animals
MH  - Brain/drug effects/metabolism
MH  - Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/pharmacology
MH  - GTP-Binding Proteins/metabolism
MH  - Ligands
MH  - Opioid Peptides/*metabolism
MH  - Pain Measurement/methods
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Opioid, mu/*metabolism
MH  - Up-Regulation/drug effects
PMC - PMC3857906
EDAT- 2013/12/19 06:00
MHDA- 2014/08/12 06:00
PMCR- 2013/11/24
CRDT- 2013/12/19 06:00
PHST- 2013/04/30 00:00 [received]
PHST- 2013/08/22 00:00 [revised]
PHST- 2013/09/06 00:00 [accepted]
PHST- 2013/12/19 06:00 [entrez]
PHST- 2013/12/19 06:00 [pubmed]
PHST- 2014/08/12 06:00 [medline]
PHST- 2013/11/24 00:00 [pmc-release]
AID - 10.1155/2013/501086 [doi]
PST - ppublish
SO  - Biomed Res Int. 2013;2013:501086. doi: 10.1155/2013/501086. Epub 2013 Nov 24.