Characterization of rat intestinal angiotensin II receptors.
In rat ileum and duodenum 125I-sarcosine1,isoleucine8-angiotensin II labels a single population of binding sites with comparable receptor densities of 98 and 94 fmol/mg protein, respectively. Radioligand binding was dose dependently antagonized by angiotensin II (AII) and related peptides. DuP 753, a selective antagonist for the angiotensin AT1 receptor subtype, potently inhibited radioligand binding in both tissues (Ki: 12.7 and 11.8 nM), while AT2-selective ligands like PD 123.177 or p-amino-phenylalanine6-AII were inactive in concentrations lower than 1 microM. The contractile response to AII (1 microM) in ileal longitudinal and circular smooth muscle preparations amounted to 96 and 16%, respectively, of the response to 100 microM methacholine. The contractile response to AII was inhibited by DuP 753 (pA2 7.53) but unaffected by PD 123.177 (pA2 less than 5). The AII effect in longitudinal duodenal preparations amounted to only 24% of the methacholine response and was totally abolished in the presence of 1 microM DuP 753. No contraction due to AII was observed in duodenal circular smooth muscle preparations. The results obtained demonstrate the existence of functional AT1 receptors in the rat ileum and duodenum. In the ileum these receptors are mainly located on the longitudinal smooth muscle and coupled to contraction. In duodenal smooth muscle AII receptors may be either less effectively coupled to contractile elements or involved in another, additional function.
Schinke
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M
Department of Pharma Research, Dr. Karl Thomae GmbH, Biberach, F.R.G.
Doods
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Ganten
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Wienen
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Entzeroth
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D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D004386:Duodenum / Q000378:metabolism; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008566:Membranes / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000032:analysis* / Q000187:drug effects
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D015059:1-Sarcosine-8-Isoleucine Angiotensin II