(/sup 3/H)-8-cyclopentyl-1,3-dipropylxanthine binding to A1 adenosine receptors of intact rat ventricular myocytes
The purpose of the present study was the identification of A1 adenosine receptors in intact rat ventricular myocytes, which are thought to mediate the negative inotropic effects of adenosine. The adenosine receptor antagonist (/sup 3/H)-8-cyclopentyl-1,3-dipropylxanthine was used as radioligand. Binding of the radioligand to intact myocytes was rapid, reversible, and saturable with a binding capacity of 40,000 binding sites per cell. The dissociation constant of the radioligand was 0.48 nM. The adenosine receptor antagonists 8-cyclopentyl-1,3-dipropylxanthine, xanthine amine congener, and theophylline were competitive inhibitors with affinities in agreement with results obtained for A1 receptors in other tissues. Competition experiments using the adenosine receptor agonists R-N(6)-phenylisopropyladenosine, 5'-N-ethylcarboxamidoadenosine, and S-N(6)-phenylisopropyladenosine gave monophasic displacement curves with Ki values of 50 nM, 440 nM, and 4,300 nM, which agreed well with the GTP-inducible low affinity state in cardiac membranes. The low affinity for agonists was not due to agonist-induced desensitization, and correlated well with the corresponding IC50 values for the inhibition of cyclic AMP accumulation by isoprenaline. It is suggested that only a low affinity state of A1 receptors can be detected in intact rat myocytes due to the presence of high concentrations of guanine nucleotides in intact cells.
- Research Organization:
- Universitaet Heidelberg (Germany, F.R.)
- OSTI ID:
- 6736721
- Journal Information:
- Circ. Res.; (United States), Journal Name: Circ. Res.; (United States) Vol. 63:3; ISSN CIRUA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ADENOSINE
AFFINITY
ANIMAL CELLS
ANIMALS
AROMATICS
AZAARENES
BIOCHEMICAL REACTION KINETICS
BODY
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
CELL MEMBRANES
HEART
HETEROCYCLIC COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIGANDS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
MUSCLES
MYOCARDIUM
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PROTEINS
PURINES
RATS
REACTION KINETICS
RECEPTORS
RIBOSIDES
RODENTS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES
XANTHINES