Molecular cloning of the canine angiotensin II receptor. An AT1-like receptor with reduced affinity for DuP753.
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.
Burns
L
L
Department of Chemical Endocrinology, St Bartholomew's Hospital Medical College, London, UK.
Clark
K L
KL
Bradley
J
J
Robertson
M J
MJ
Clark
A J
AJ
D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001483:Base Sequence; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA; D004285:Dogs; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D019808:Losartan; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular; D011817:Rabbits; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D004247:DNA; D019808:Losartan