Abstract
Canine aortic strip studies revealed insensitivity of angiotensin II (AII)-induced aortic contraction to inhibition by the non-peptide antagonist DuP753 (pKB = 6.7 +/- 0.1). In order to determine the origin of this phenomenon we cloned the canine homologue of the AT1 AII receptor. Expression of this cDNA in COS-7 cells indicated a low affinity of DuP753 for the cloned receptor (KD = 92 nM). The predicted amino acid sequence is highly homologous to other mammalian AT1 receptors; sequence comparisons suggest the pharmacological difference may be the result of a threonine residue in position 163 in the IVth transmembrane domain.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Angiotensin II / antagonists & inhibitors*
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Angiotensin Receptor Antagonists
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Animals
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Aorta / drug effects
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Base Sequence
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Biphenyl Compounds / pharmacology*
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Cell Line
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Cloning, Molecular
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DNA
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Dogs
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Humans
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Imidazoles / pharmacology*
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In Vitro Techniques
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Losartan
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Molecular Sequence Data
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Muscle Contraction / drug effects
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Muscle, Smooth, Vascular
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Rabbits
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Receptors, Angiotensin / drug effects
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Receptors, Angiotensin / genetics*
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Sequence Homology, Amino Acid
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Tetrazoles / pharmacology*
Substances
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Angiotensin Receptor Antagonists
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Biphenyl Compounds
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Imidazoles
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Receptors, Angiotensin
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Tetrazoles
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Angiotensin II
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DNA
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Losartan