A cloned angiotensin receptor isoform from the turkey adrenal gland is pharmacologically distinct from mammalian angiotensin receptors

T. J. Murphy, Y. Nakamura, K. Takeuchi, R. W. Alexander

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)

Abstract

A 2046-base pair cDNA clone, homologous to mammalian angiotensin (AT) AT1 receptors, was isolated from a library prepared from adrenal glands of the domestic turkey (Meleagris gallopavo). Sequence analysis of the cDNA insert in clone pTAT2' reveals a 1077-base pair open reading frame predicting a 359- amino acid protein ~75% homologous to mammalian AT1 receptors. Saturation radioligand binding studies performed in membranes of COS-7 cells transfected with pTAT2' show high affinity specific binding of 125I-angiotensin II, with a K(d) of 172 pM. The rank order of affinities for a series of ligands determined by competition binding studies is angiotensin II ≥ [Sar1,Ile8]- angiotensin II > angiotensin II ≃ [Sar1,Ala8]-angiotensin II ≃ CGP42112A > angiotensin I> Dup753 > PD123177. This rank order of affinity series differs substantially from that for mammalian AT1 receptors and AT2 binding sites. Angiotensin II (100 nM) can stimulate inositol phosphate production similarily in COS-7 cells transfected with pTAT2' and in COS-7 cells transfected with the AT(1a) receptor cDNA pCa18b. This response in pTAT2'- transfected cells is not attenuated in the presence of 30 μM Dup753. In contrast, this concentration of antagonist attenuates >90% of the inositol phosphate response to angiotensin II in COS-7 cells transfected with the rat AT(1a) receptor cDNA. These results demonstrate an avian structural homologue of mammalian AT1 receptors possessing distinct pharmacological properties with both peptide and nonpeptide AT receptor ligands.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalMolecular pharmacology
Volume44
Issue number1
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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