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Photoaffinity labeling the. beta. -adrenergic receptor with an iodoazido derivative of norepinephrine

Thesis/Dissertation ·
OSTI ID:5527108
The {beta}-adrenergic receptor is an integral membrane protein coupled to adenylate cyclase by the guanine nucleotide binding protein, Gs. Agonist binding to the receptor results in coupling the receptor to Gs, increased adenylate cyclase activity, and receptor desensitization. In contrast, antagonists bind but do not activate the receptor or result in desensitization. To study the structure and regulation of the {beta}-adrenergic receptor in the membrane, it is useful to develop ligands which covalently label the binding site. In this thesis the synthesis and characterization of the first agonist photolabel for the {beta}-adrenergic receptor is presented. The agonist photoaffinity label, N-(p-azido-m-iodophenethylamidoisobutyl)-norepinephrine (NAIN), was synthesized in non-radioactive and radioactive carrier-free forms with {sup 125}I (2,200 Ci/mmole). NAIN was chemically characterized by TLC mobility, melting point, NMR, IR, and Mass Spectroscopy. NAIN was shown to be competitive with the {beta}-adrenergic ligand ({sup 125}I)-ICYP in several membranes containing {beta}-adrenergic receptors. Binding data indicated that NAIN coupled the receptor to Gs and had an affinity for the receptor which was similar to isoproterenol. NAIN stimulated adenylate cyclase activity in guinea pig lung and S49 WT mouse lymphoma cell membranes with a K{sub act} and V max similar to isoproterenol while in frog erythrocyte ghosts, NAIN produced 77% of the maximally stimulated adenylate cyclase activity of isoproterenol. These data show that NAIN is an agonist for the {beta}-adrenergic receptor.
Research Organization:
Wisconsin Univ., Madison, WI (USA)
OSTI ID:
5527108
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CELL MEMBRANES
CHEMICAL COMPOSITION
CHROMATOGRAPHY
CYCLASES
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
GUINEA PIGS
HORMONES
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLING
LIGANDS
LYASES
MAMMALS
MASS SPECTRA
MEMBRANE PROTEINS
MEMBRANES
MOLECULAR STRUCTURE
NEUROREGULATORS
NMR SPECTRA
NORADRENALINE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RODENTS
SEPARATION PROCESSES
SPECTRA
SYMPATHOMIMETICS
THIN-LAYER CHROMATOGRAPHY
TRACER TECHNIQUES
VERTEBRATES