| Literature DB >> 8058755 |
E H Ohlstein1, P Nambi, S A Douglas, R M Edwards, M Gellai, A Lago, J D Leber, R D Cousins, A Gao, J S Frazee.
Abstract
An extremely potent and highly specific non-peptide, subnanomolar endothelin (ET) receptor antagonist, SB 209670, has been synthesized and characterized. SB 209670, which was rationally designed using conformational models of ET-1, selectively inhibits binding of 125I-labeled ET-1 to cloned human ET receptor subtypes ETA and ETB (Ki = 0.2 and 18 nM, respectively). SB 209670 produces concentration-dependent inhibition of ET-1-mediated vasoconstriction in isolated vascular tissues and in vivo following either intravenous or intraduodenal administration. SB 209670 produces a dose-dependent reduction in blood pressure in hypertensive rats, protects from ischemia-induced neuronal degeneration in a gerbil stroke model, and attenuates neointima formation following rat carotid artery balloon angioplasty. SB 209670 will be useful in characterizing and classifying the physiological and pathophysiological effects of ET.Entities:
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Year: 1994 PMID： 8058755 PMCID： PMC44543 DOI： 10.1073/pnas.91.17.8052
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205