PMID- 1668109
OWN - NLM
STAT- MEDLINE
DCOM- 19920730
LR  - 20190814
IS  - 0024-4201 (Print)
IS  - 0024-4201 (Linking)
VI  - 26
IP  - 12
DP  - 1991 Dec
TI  - L-659,989: a useful probe in the detection of multiple conformational states of 
      PAF receptors.
PG  - 1148-53
AB  - L-659,989 is a potent, specific and competitive platelet-activating factor (PAF) 
      receptor antagonist. The 2,5-tritium labeled L-659,989, similar to [3H]PAF, 
      specifically binds to rabbit platelet membranes with an equilibrium dissociation 
      constant (KD) of 1.60 (+/- 0.20) nM in 10 mM MgCl2. However, guanosine 
      5'-triphosphate (GTP) and several cations affect the specific binding of [3H]PAF 
      and of [3H]L-659,989 to rabbit platelet membranes in different ways. K+, Mg2+, 
      Ca2+ and Mn2+ potentiate the specific binding of both ligands. Na+ and Li+ 
      inhibit the specific [3H]PAF binding, but enhance the binding of [3H]L-659,989; 
      GTP reduces the [3H]PAF binding but has no effect on the binding of 
      [3H]-L-659,989. Ni2+ inhibits the [3H]L-659-989 binding, but has no effect on the 
      binding of [3H]PAF. In the presence of 150 mM NaCl, [3H]L-659,989 exhibits 
      identical KD and detectable binding sites (Bmax) values as those in the presence 
      of 10 mM MgCl2, while KD And Bmax values of [3H]PAF are dramatically reduced in 
      the presence of 150 mM NaCl compared to those in 10 mM MgCl2. These results 
      suggest the existence of multiple conformational states of the PAF specific 
      receptor and that PAF and L-659,989 bind differently to those states. In the 
      presence of 150 mM NaCl and 1 mM GTP, receptors appear to exist in a single 
      conformational state with an equilibrium dissociation constant (KB) of 0.93 
      microM for PAF as derived from the Schild plot. In isolated rabbit platelets 
      pretreated with 10 microM ETH 227, a Na(+)-specific ionophore, the detectable 
      [3H]PAF binding sites drop from 260 to 100 binding sites per platelet, but the 
      binding sites for [3H]L-659,989 remain roughly the same. The Na+ binding sites 
      which modulate the conformation of PAF receptors are therefore protected from 
      extracellular Na+ until ionophore is added, and are probably located on the 
      cytoplasmic side of the plasma membrane.
FAU - Hwang, S B
AU  - Hwang SB
AD  - Merck Sharp & Dohme Research Laboratories, Department of Biochemical Regulation, 
      Rahway, New Jersey 07065-0900.
FAU - Lam, M H
AU  - Lam MH
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Lipids
JT  - Lipids
JID - 0060450
RN  - 0 (Furans)
RN  - 0 (Platelet Activating Factor)
RN  - 0 (Platelet Membrane Glycoproteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (platelet activating factor receptor)
RN  - 129314-27-8 (L 659989)
RN  - 42EWD89I80 (1-hexadecyl-2-acetyl-glycero-3-phosphocholine)
SB  - IM
MH  - Animals
MH  - Binding, Competitive
MH  - Blood Platelets/*metabolism
MH  - Cell Membrane/metabolism
MH  - Furans/*pharmacology
MH  - Humans
MH  - Kinetics
MH  - Models, Biological
MH  - Platelet Activating Factor/analogs & derivatives/*metabolism
MH  - *Platelet Membrane Glycoproteins
MH  - Protein Conformation
MH  - Rabbits
MH  - Receptors, Cell Surface/antagonists & inhibitors/chemistry/*metabolism
MH  - *Receptors, G-Protein-Coupled
RF  - 22
EDAT- 1991/12/01 00:00
MHDA- 1991/12/01 00:01
CRDT- 1991/12/01 00:00
PHST- 1991/12/01 00:00 [pubmed]
PHST- 1991/12/01 00:01 [medline]
PHST- 1991/12/01 00:00 [entrez]
AID - 10.1007/BF02536520 [doi]
PST - ppublish
SO  - Lipids. 1991 Dec;26(12):1148-53. doi: 10.1007/BF02536520.