Synthesis and characterization of new adenosine A/sub 1/ receptor radioligands, N/sup 6/-3-/sup 125/IODO-4-aminobenzyladenosine, and a photoaffinity probe, N/sup 6/-3-/sup 125/IODO-4-azidobenzyladenosine

Thesis/Dissertation · Wed Jan 01 04:00:00 EST 1986

OSTI ID:5559040

Patel, A P

Characterization of adenosine receptors in brain and fat membranes has been achieved with /sup 3/H-cyclohexyladenosine, /sup 125/Iodohydroxyphenylisopropyladenosine (/sup 125/IHPIA) and other radioligands. However, these radioligands failed to label cardiac receptors. The authors have synthesized two new radioligands, /sup 125/Iodoaminobenzyladenosine (/sup 125/IABA), and a photoaffinity probe /sup 125/Iodoazidobenzyladenosine (/sup 125/IAzBA). /sup 125/IABA bound to a single class of adenosine receptors on rat ventricle membranes with a K/sub D/ equivalent to that of /sup 125/IHPIA and Bmax of 15.2 fmol/mg protein but with one-sixth the nonspecific binding of the other radioligand. In brain membranes, /sup 125/IABA bound with a higher affinity (K/sub D/ 1.93 nM) than in the heart membranes (K/sub D/ 11.6 nM). Iodination of aminobenzyladenosine increased affinity for the adenosine receptor by 22-fold; from studies on adenylate cyclase in adipocytes and chick heart cells, the new ligand was found to be a full agonist at an A/sub 1/ adenosine receptor. /sup 125/Iodoazidobenzyladenosine (/sup 125/IAzBA) bound with high affinity (K/sub D/-1nM); to receptors on cortical membranes from dog, rat, guinea pig and pig. On photolysis, /sup 125/IAzBA on the adenosine receptor was covalently incorporated into a receptor binding subunit with a Mr of 34 kDa. /sup 125/IAzBA specifically photoincorporated into 34 kDa peptide in dog, guinea pig, rat, chick and pig cortical membranes; and in rat fat membranes. These results suggest that the A/sub 1/ adenosine receptor binding subunit in various mammalian species and tissues resides on a 34 kDa protein.

• Research Organization: Oklahoma Univ., Oklahoma City (USA). Health Sciences Center
• OSTI ID: 5559040
• Country of Publication: United States
• Language: English

Related Subjects

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
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62 RADIOLOGY AND NUCLEAR MEDICINE
ADENOSINE
ADIPOSE TISSUE
ANIMAL TISSUES
ANIMALS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
CHEMICAL PREPARATION
CHEMICAL REACTIONS
CONNECTIVE TISSUE
DAYS LIVING RADIOISOTOPES
DOGS
DOMESTIC ANIMALS
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
GUINEA PIGS
HALOGENATION
INTERMEDIATE MASS NUCLEI
IODINATION
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LIGANDS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
NUCLEI
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC IODINE COMPOUNDS
ORGANS
PROTEINS
RADIOISOTOPES
RADIOPHARMACEUTICALS
RADIORECEPTOR ASSAY
RATS
REACTION KINETICS
RECEPTORS
RIBOSIDES
RODENTS
SWINE
SYNTHESIS
TISSUES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES