PMID- 10516632
OWN - NLM
STAT- MEDLINE
DCOM- 19991222
LR  - 20181113
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 128
IP  - 3
DP  - 1999 Oct
TI  - Constitutive activity of the delta-opioid receptor expressed in C6 glioma cells: 
      identification of non-peptide delta-inverse agonists.
PG  - 556-62
AB  - 1. G-protein coupled receptors can exhibit constitutive activity resulting in the 
      formation of active ternary complexes in the absence of an agonist. In this study 
      we have investigated constitutive activity in C6 glioma cells expressing either 
      the cloned delta-(OP1) receptor (C6delta), or the cloned mu-(OP3) opioid receptor 
      (C6mu). 2. Constitutive activity was measured in the absence of Na+ ions to 
      provide an increased signal. The degree of constitutive activity was defined as 
      the level of [35S]-GTPgammaS binding that could be inhibited by pre-treatment 
      with pertussis toxin (PTX). In C6delta cells the level of basal [35S]-GTPgammaS 
      binding was reduced by 51.9+/-6.1 fmols mg-1 protein, whereas in C6mu; and C6 
      wild-type cells treatment with PTX reduced basal [35S]-GTPgammaS binding by only 
      10.0+/-3.5 and 8.6+/-3.1 fmols mg-1 protein respectively. 3. The 
      delta-antagonists N, N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI 174,864), 
      7-benzylidenenaltrexone (BNTX) and naltriben (NTB), in addition to clocinnamox 
      (C-CAM), acted as delta-opioid receptor inverse agonists. Naloxone, 
      buprenorphine, and naltrindole were neutral antagonists. Furthermore, naltrindole 
      blocked the reduction in [35S]-GTPgammaS binding caused by the inverse agonists. 
      The inverse agonists did not inhibit basal [35S]-GTPgammaS binding in C6mu; or C6 
      wild-type cell membranes. 4. Competition binding assays in C6delta cell membranes 
      revealed a leftward shift in the displacement curve of [3H]-naltrindole by ICI 
      174,864 and C-CAM in the presence of NaCl and the GTP analogue, GppNHp. There was 
      no change in the displacement curve for BNTX or NTB under these conditions. 5. 
      These data confirm the presence of constitutive activity associated with the 
      delta-opioid receptor and identify three novel, non-peptide, delta-opioid inverse 
      agonists.
FAU - Neilan, C L
AU  - Neilan CL
AD  - Department of Pharmacology, University of Michigan Medical School, 1301 MSRB III, 
      Ann Arbor, Michigan, MI 48109-0632, USA.
FAU - Akil, H
AU  - Akil H
FAU - Woods, J H
AU  - Woods JH
FAU - Traynor, J R
AU  - Traynor JR
LA  - eng
GR  - DA 00254/DA/NIDA NIH HHS/United States
GR  - P01 DA000254/DA/NIDA NIH HHS/United States
GR  - DA 02265/DA/NIDA NIH HHS/United States
GR  - K21 DA000254/DA/NIDA NIH HHS/United States
GR  - P50 DA000254/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Narcotic Antagonists)
RN  - 0 (Receptors, Opioid, delta)
RN  - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate))
SB  - IM
MH  - Animals
MH  - Guanosine 5'-O-(3-Thiotriphosphate)/metabolism
MH  - Narcotic Antagonists/metabolism
MH  - Radioligand Assay
MH  - Rats
MH  - Receptors, Opioid, delta/antagonists & inhibitors/*metabolism
MH  - Tumor Cells, Cultured
PMC - PMC1571659
EDAT- 1999/10/12 00:00
MHDA- 1999/10/12 00:01
PMCR- 2000/10/01
CRDT- 1999/10/12 00:00
PHST- 1999/10/12 00:00 [pubmed]
PHST- 1999/10/12 00:01 [medline]
PHST- 1999/10/12 00:00 [entrez]
PHST- 2000/10/01 00:00 [pmc-release]
AID - 0702816 [pii]
AID - 10.1038/sj.bjp.0702816 [doi]
PST - ppublish
SO  - Br J Pharmacol. 1999 Oct;128(3):556-62. doi: 10.1038/sj.bjp.0702816.