The cardiac β-adrenergic receptor. Structural similarities of β1 and β2 receptor subtypes demonstrated by photoaffinity labeling

G. L. Stiles, R. H. Strasser, T. N. Lavin, L. R. Jones, M. G. Caron, R. J. Lefkowitz

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

The β-adrenergic receptor photoaffinity ligand p-azido-m-[125I]iodobenzylcarazolol has been used to covalently label the β1 and β2 adrenergic receptor binding subunits present in left ventricular myocardial membranes derived from mammalian (including human) and nonmammalian species. Covalent incorporation of the photoaffinity ligand into membrane proteins was followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In the case of the human, canine, porcine, rabbit, and rat left ventricle, all of which contain predominantly or exclusively β1-adrenergic receptors, two peptides of M(r) ≃ 62,000 (major component) and M(r) ≃ 55,000 (minor component) were specifically labeled and visualized by autoradiography. Photoincorporation into these two bands could be blocked with the appropriate drugs to display a β1-adrenergic receptor pharmacological specificity. Simultaneous sodium dodecyl sulfate-polyacrylamide gel electrophoresis of samples from each species revealed that all of the M(r) = 62,000 peptides co-migrated suggesting similarity in the β1-adrenergic receptor binding subunit peptides in all of these species. The minor component M(r) ≃ 55,000 appears to be a proteolytic degradation product of the M(r) = 62,000 peptide. Its formation could be decreased by proteinase inhibitors. This suggests that the heterogeneity of the labeling pattern observed in mammalian tissues in this and previous studies may be the result of proteolytic degradation of the receptor subunit which occurs during membrane preparation. Photoaffinity labeling of frog ventricular membranes which contain predominantly β2-adrenergic receptors also revealed two peptides of M(r) ≃ 62,000 (major component) and 55,000 (minor component) with the pharmacological selectivity of a β2-adrenergic receptor. These data suggest marked similarities in the β1- and β2-adrenergic receptor binding subunits of different species and suggest that the pharmacological subtype might be determined by the detailed structure, i.e. amino acid sequence, at the ligand binding sites of the receptor peptide.

Original languageEnglish (US)
Pages (from-to)8443-8449
Number of pages7
JournalJournal of Biological Chemistry
Volume258
Issue number13
StatePublished - Dec 1 1983
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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