First Reported Nonpeptide AT1 Receptor Agonist (L-162,313) Acts as an AT2 Receptor Agonist in Vivo
2004 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 47, no 6, 1536-1546 p.Article in journal (Refereed) Published
In this investigation, it is demonstrated that the first nonpeptide AT1 receptor agonist L-162,313 (1), disclosed in 1994, also acts as an agonist at the AT2 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 AT2 receptor antagonist PD-123,319. The data strongly suggest that 1 is an AT2 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 AT2 receptor.
Place, publisher, year, edition, pages
2004. Vol. 47, no 6, 1536-1546 p.
Angiotensin II Type 1 Receptor Blockers, Animals, Binding; Competitive, Biphenyl Compounds/*pharmacology, Duodenum/drug effects/secretion, Female, Imidazoles/*pharmacology, In Vitro, Intestinal Mucosa/drug effects/secretion, Male, Myometrium/metabolism, Pyridines/pharmacology, Radioligand Assay, Rats, Rats; Sprague-Dawley, Receptor; Angiotensin; Type 1/agonists, Receptor; Angiotensin; Type 2/*agonists/antagonists & inhibitors, Research Support; Non-U.S. Gov't, Swine
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-97462DOI: 10.1021/jm031031iPubMedID: 14998339OAI: oai:DiVA.org:uu-97462DiVA: diva2:172422