(/sup 125/I)Aminobenzyladenosine, a new radioligand with improved specific binding to adenosine receptors in heart

Journal Article · Fri Feb 01 04:00:00 EST 1985 · Circ. Res.; (United States)

DOI:https://doi.org/10.1161/01.RES.56.2.279· OSTI ID:5613083

Linden, J; Patel, A; Sadek, S

The density of adenosine receptors in membranes derived from rat hearts in 25 times lower than the density of receptors in rat brain membranes. Consequently, adenosine radioligands which are useful in brain such as l-(/sup 3/H)phenylisopropyladenosine, (/sup 3/H)cyclohexyladenosine, (/sup 3/H)-2-chloroadenosine and l-(/sup 125/I)hydroxyphenylisopropyladenosine are of limited usefulness in heart, due to a high ratio of nonspecific to specific binding. We have synthesized a new radioligand, (/sup 125/I)-N6-4-aminobenzyladenosine, which binds to rat heart membranes with one-sixth the nonspecific binding of the other radioligands. (/sup 125/I)-N6-4-aminobenzyladenosine bound to rat ventricle membranes with a K/sub D/ equivalent to that of l-(/sup 125/I)hydroxyphenylisopropyladenosine and a B/sub max/ of 15.2 fmol/mg protein. (/sup 125/I)-N6-4-aminobenzyladenosine bound with a higher affinity to brain (K/sub D/ . 1.93 nM) than to heart membranes (K/sub D/ . 11.6 nM). At the radioligand K/sub D/, 60% of the total (/sup 125/I)-N6-4-aminobenzyladenosine bound to heart membranes was specifically bound. Iodination of aminobenzyladenosine increased its affinity for the adenosine receptor by 22-fold, possibly due to a steric or hydrophobic effect of iodine. The new ligand was found to be a full adenosine agonist based on its ability to inhibit cyclic adenosinemonophosphate accumulation in isolated embryonic chick heart cells and rat adipocytes. (/sup 125/I)-N6-4-Aminobenzyladenosine bound to a single affinity site and was displaced from cardiac and brain adenosine receptors by other adenosine analogues with a potency order of l-phenylisopropyladenosine greater than 5'-N-ethylcarboxamide adenosine. These characteristics suggest that the radioligand binds to an Ri adenosine receptor.

• Research Organization: Oklahoma Medical Research Foundation, Oklahoma City
• OSTI ID: 5613083
• Journal Information: Circ. Res.; (United States), Journal Name: Circ. Res.; (United States) Vol. 56:2; ISSN CIRUA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADENOSINE
AMP
ANIMALS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CHEMICAL PREPARATION
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
HEART
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LABELLING
MAMMALS
MEMBRANES
NERVOUS SYSTEM
NUCLEI
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
RADIOISOTOPES
RATS
REACTION KINETICS
RECEPTORS
RIBOSIDES
RODENTS
SYNTHESIS
VERTEBRATES