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

研究成果: Article査読

60 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1-7
ページ数7
ジャーナルMolecular pharmacology
44
1
出版ステータスPublished - 1993

ASJC Scopus subject areas

  • 分子医療
  • 薬理学

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