Development of a photolabile ligand for the endothelin-A receptor of endothelin.
Actions of endothelin (ET) are usually mediated through the so-called endothelin-A or -B (ET(A) or ET(B))-receptors. As part of our ongoing research program, we are studying the characterization of the ET(A)-receptor using specific photolabile ligands. Starting with the ET(A)-specific antagonist TTA-386 as a leading compound we developed new ET(A)-specific antagonists containing the photolabile amino acid, p-benzoyl-phenylalanine (Bpa). Following a Bpa peptide scan, with either the L- or D-isomer, we found that D-phenylalanine-6 of TTA-386 can be substituted with either L- or D-Bpa and gives analogs showing antagonistic properties, in an ET(A)-receptor preparation (rat aorta), very similar to those of TTA-386 itself. No agonistic or antagonistic properties were measured with these derivatives in an ET(B) pharmacological preparation (guinea pig lung parenchyma). Thus, these new ligands appear as very promising probes for the characterization of the ET(A)-receptor.
Tessier
S
S
Centre of Research in Human Health, INRS/Armand-Frappier Institute, University of Québec, Pointe-Claire, Canada.
Langlois
C
C
Brkovic
A
A
Coupal
M
M
De Léan
A
A
Fournier
A
A
D000818:Animals; D065128:Endothelin Receptor Antagonists; D066298:In Vitro Techniques; D008024:Ligands; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
D065128:Endothelin Receptor Antagonists; D008024:Ligands; D009842:Oligopeptides; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; C108845:TTA 386