Abstract
In this investigation, it is demonstrated that the first nonpeptide AT(1) receptor agonist L-162,313 (1), disclosed in 1994, also acts as an agonist at the AT(2) receptor. In anesthetized rats, administration of compound 1 intravenously or locally in the duodenum increased duodenal mucosal alkaline secretion, effects that were sensitive to the selective AT(2) receptor antagonist PD-123,319. The data strongly suggest that 1 is an AT(2) receptor agonist in vivo. To the best of our knowledge, this substance is the first nonpeptidic low-molecular weight compound with an agonistic effect mediated through the AT(2) receptor.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiotensin II Type 1 Receptor Blockers
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Angiotensin II Type 2 Receptor Blockers
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Animals
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Binding, Competitive
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Biphenyl Compounds / pharmacology*
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Duodenum / drug effects
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Duodenum / metabolism
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Female
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Imidazoles / pharmacology*
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In Vitro Techniques
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Intestinal Mucosa / drug effects
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Intestinal Mucosa / metabolism
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Male
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Myometrium / metabolism
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Pyridines / pharmacology
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Radioligand Assay
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Rats
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Rats, Sprague-Dawley
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Receptor, Angiotensin, Type 1 / agonists
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Receptor, Angiotensin, Type 2 / agonists*
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Swine
Substances
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Angiotensin II Type 1 Receptor Blockers
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Angiotensin II Type 2 Receptor Blockers
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Biphenyl Compounds
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Imidazoles
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L 162313
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Pyridines
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Receptor, Angiotensin, Type 1
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Receptor, Angiotensin, Type 2
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PD 123319