Abstract
Photoaffinity labeling techniques using p-azido-m-[125I]iodobenzylcarazolol have recently demonstrated that both the beta 1- and beta 2-adrenergic receptor-binding subunits from mammalian tissues including heart, lung, and erythrocytes reside on peptides of Mr approximately equal to 62,000-64,000. In this study, a two-dimensional gel electrophoresis method for peptide mapping was used to investigate and compare the structure of beta 1 - and beta 2-adrenergic receptor subtypes. When the photoaffinity labeled Mr approximately equal to 62,000 peptides from the beta 2-adrenergic receptors of rat lung and erythrocyte are subjected to simultaneous proteolysis using Staphylococcus aureus V8 proteinase or papain, exactly the same peptide fragments are generated from each subunit. In contrast, when the Mr approximately equal to 62,000 peptide containing the beta 1-adrenergic receptor-binding subunit derived from the rat heart is proteolyzed simultaneously with the Mr approximately equal to 62,000 peptide containing the beta 2-adrenergic receptors from either lung or erythrocyte, the peptide fragments generated are distinctly different. Peptide maps of beta 1-adrenergic receptors from the myocardial tissue of different species (pig versus rat) yield slightly different maps while the maps derived from the beta 2-adrenergic receptors of hamster lung and rat lung or erythrocytes reveal no interspecies differences. These data suggest: 1) alterations in the primary structure of the beta-adrenergic receptor may be responsible for the pharmacological specificities characteristic of beta 1- and beta 2-adrenergic receptor subtypes; and 2) alterations in the primary structure of similar beta-adrenergic receptor subtypes across different species may relate to the magnitude of their phylogenetic differences.
Highlights
From the Howard Hughes Medical Institute, Departmentsof Medicine (Cardiology), Biochemistry, and Physiology, Duke University Medical Center, Durham, North Carolin2a7710
[‘2SI]iodobenzylcarazolol have recently demonstrated selectively greater affinity for one or the other of the two,B-. That both the & - and &-adrenergic receptor-binding receptor subtypes have been developed. It hasbeen proposed subunitsfrom mammaliantissuesincluding heart, that P,adrenergic receptors evolved as synaptic receptorsfor lung,anderythrocytesreside on peptidesof M, p the sympathetic neurotransmitter norepinephriwnehereas p2
/3-adrenergic receptors with specific high affinity radioactive photoaffinity probes such as [1251]pABC’(2-4). These techniqueshave demonstrated that both PI- and pz-adrenergic receptor-binding subunits from mammalian tissuesincluding heart, lung, anderythrocytes reside on a peptide of M, =
Summary
Vol 258, No 17, h u e of September 10, pp, 10689-10694,1983 Printed m U.S.A. From the Howard Hughes Medical Institute, Departmentsof Medicine (Cardiology), Biochemistry, and Physiology, Duke University Medical Center, Durham, North Carolin2a7710. That both the & - and &-adrenergic receptor-binding receptor subtypes have been developed. /3-adrenergic receptors with specific high affinity radioactive photoaffinity probes such as [1251]pABC’(2-4). These techniqueshave demonstrated that both PI- and pz-adrenergic receptor-binding subunits from mammalian tissuesincluding heart, lung, anderythrocytes reside on a peptide of M , =. Rocyte, the peptide fragments generated are distinctly In order to explore and compare the detailed structure of different.Peptidemaps of B1-adrenergicreceptors PI- and &adrenergic receptor peptides, we have adapted the from the myocardial tissue of different species(pig methodology of Bordier and Crettol-Jarvinen [5] for peptide uersus rat) yield slightly different maps while the mmapaspping to assespsossible homologies in the structureof two derived from the B2-adrenergic receptors of hamster subtypes of P-adrenergic receptors. These data suggest: 1) alterations in of a given receptor subtype identical across different tissues the primary structuorfethe @-adrenergic recepmtoary within a single species? Second, within a species do Dl- and ol- beresponsible forthe pharmacologicalspecificities &-adrenergic receptors differ in structure? does the ctsyihmpaerisala;crtaenr&disat2dic)reaonlfteerrgaitciaonnrdesc,ie&np-ttaohdrerepsnrueibmrgtayicrpyerssetcreaupccrttooursrsseubdo-ifffersmetranulticatnursepeocfieas?receptor subtype differ across different mamspecies may relate to the magnitudeof their phylogenetic differences
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