Actions of endothelin (ET) are usually mediated through the so-called endothelin-A or -B (ETA or ETB)-receptors. As part of our ongoing research program, we are studying the characterization of the ETA-receptor using specific photolabile ligands. Starting with the ETA-specific antagonist TTA-386 as a leading compound we developed new ETA-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 ETA-receptor preparation (rat aorta), very similar to those of TTA-386 itself. No agonistic or antagonistic properties were measured with these derivatives in an ETB pharmacological preparation (guinea pig lung parenchyma). Thus, these new ligands appear as very promising probes for the characterization of the ETA-receptor.
Centre of Research in Human Health, INRS/Armand-Frappier Institute, University of Québec, Pointe-Claire, QC, Canada and *Department of Pharmacology, University of Montréal, QC, Canada
Address correspondence and reprint requests to Dr Alain Fournier, INRS/Institut Armand-Frappier, Université du Québec, 245 boulevard Hymus, Pointe-Claire, Québec, Canada, H9R 1G6.
© 2000 Lippincott Williams & Wilkins, Inc.