PMID- 17622576
OWN - NLM
STAT- MEDLINE
DCOM- 20071127
LR  - 20231213
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 72
IP  - 4
DP  - 2007 Oct
TI  - Identification of regions of the sigma-1 receptor ligand binding site using a 
      novel photoprobe.
PG  - 921-33
AB  - sigma Receptors, once considered a class of opioid receptors, are now regarded as 
      a unique class of receptors that contain binding sites for a wide range of 
      ligands, including the drug 1-N(2',6'-dimethylmorpholino)3-(4-t-butylpropylamine) 
      (fenpropimorph), a yeast sterol isomerase inhibitor. Because fenpropimorph has 
      high-binding affinity to the sigma-1 receptor, we have synthesized a series of 
      fenpropimorph-like derivatives with varying phenyl ring substituents and have 
      characterized their binding affinities to the sigma-1 receptor. In addition, we 
      have synthesized a carrier-free, radioiodinated fenpropimorph-like photoaffinity 
      label, 1-N-(2',6'-dimethyl-morpholino)-3-(4-azido-3-[(125)I]iodo-phenyl)propane 
      ([(125)I]IAF), which covalently derivatized the sigma-1 receptor (25.3 kDa) in 
      both the rat liver and guinea pig liver membranes and the sigma-2 receptor (18 
      kDa) in rat liver membranes with high specificity. Furthermore, after cleaving 
      the specific [(125)I]IAF-photolabeled sigma-1 receptor in guinea pig and rat 
      liver membranes and the pure guinea pig sigma-1 receptor with EndoLys-C and 
      cyanogen bromide, the [(125)I]IAF label was identified both in a peptide 
      containing steroid binding domain-like I (SBDLI) (amino acids 91-109) and in a 
      peptide containing steroid binding domain-like II (SBDLII) (amino acids 176-194). 
      Because a single population of binding sites (R(2) = 0.992) for [(125)I]IAF 
      interaction with the sigma-1 receptor was identified by (+)-[(3)H]pentazocine 
      competitive binding with nonradioactive [(127)I]IAF, it was concluded that SBDLI 
      (amino acids 91-109) and SBDLII (amino acids 176-194) comprises, at least in 
      part, regions of the sigma-1 receptor ligand binding site(s).
FAU - Pal, Arindam
AU  - Pal A
AD  - Department of Pharmacology, University of Wisconsin Medical School, 1300 
      University Avenue, Madison, WI 53706, USA.
FAU - Hajipour, Abdol R
AU  - Hajipour AR
FAU - Fontanilla, Dominique
AU  - Fontanilla D
FAU - Ramachandran, Subramaniam
AU  - Ramachandran S
FAU - Chu, Uyen B
AU  - Chu UB
FAU - Mavlyutov, Timur
AU  - Mavlyutov T
FAU - Ruoho, Arnold E
AU  - Ruoho AE
LA  - eng
GR  - R01-MH065503/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070710
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Ligands)
RN  - 0 (Molecular Probes)
RN  - 0 (Morpholines)
RN  - 0 (Photoaffinity Labels)
RN  - 0 (Receptors, sigma)
RN  - 4548UM725F (fenpropimorph)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Guinea Pigs
MH  - Ligands
MH  - Microsomes, Liver/metabolism
MH  - *Molecular Probes
MH  - Morpholines/metabolism/pharmacology
MH  - Nuclear Magnetic Resonance, Biomolecular
MH  - *Photoaffinity Labels
MH  - Rats
MH  - Receptors, sigma/*metabolism
MH  - Sigma-1 Receptor
EDAT- 2007/07/12 09:00
MHDA- 2007/12/06 09:00
CRDT- 2007/07/12 09:00
PHST- 2007/07/12 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2007/07/12 09:00 [entrez]
AID - mol.107.038307 [pii]
AID - 10.1124/mol.107.038307 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2007 Oct;72(4):921-33. doi: 10.1124/mol.107.038307. Epub 2007 Jul 
      10.