( sup 3 H)CGS 21680, a selective A2 adenosine receptor agonist directly labels A2 receptors in rat brain

Journal Article · Fri Dec 01 00:00:00 EST 1989 · Journal of Pharmacology and Experimental Therapeutics; (USA)

OSTI ID:7244668

Jarvis, M F; Schulz, R; Hutchison, A J; Do, U H; Sills, M A; Williams, M ^[1]

---

1. CIBA-GEIGY Corporation, Summit, NJ (USA)

In the present study, the binding of a highly A2-selective agonist radioligand, (3H)CGS 21680 (2-(p-(2-carboxyethyl)-phenethylamino)-5'-N-ethylcarboxamido adenosine) is described. (3H)CGS 21680 specific binding to rat striatal membranes was saturable, reversible and dependent upon protein concentration. Saturation studies revealed that (3H)CGS 21680 bound with high affinity (Kd = 15.5 nM) and limited capacity (apparent Bmax = 375 fmol/mg of protein) to a single class of recognition sites. Estimates of ligand affinity (16 nM) determined from association and dissociation kinetic experiments were in close agreement with the results from the saturation studies. (3H)CGS 21680 binding was greatest in striatal membranes with negligible specific binding obtained in rat cortical membranes. Adenosine agonists ligands competed for the binding of 5 nM (3H)CGS 21680 to striatal membranes with the following order of activity; CGS 21680 = 5'-N-ethylcarboxamidoadenosine greater than 2-phenylaminoadenosine (CV-1808) = 5'-N-methylcarboxamidoadenosine = 2-chloroadenosine greater than R-phenylisopropyladenosine greater than N6-cyclohexyladenosine greater than N6cyclopentyltheophylline greater than S-phenylisopropyladenosine. The nonxanthine adenosine antagonist, CGS 15943A, was the most active compound in inhibiting the binding of (3H)CGS 21680. Other adenosine antagonists inhibited binding in the following order; xanthine amine congener = 1,3-dipropyl-8-(2-amino-4-chloro)phenylxanthine greater than 1,3-dipropyl-8-cyclopentylxanthine greater than 1,3-diethyl-8-phenylxanthine greater than 8-phenyltheophylline greater than 8-cyclopentyltheophylline = xanthine carboxylic acid congener greater than 8-parasulfophenyltheophylline greater than theophylline greater than caffeine.

• OSTI ID: 7244668
• Journal Information: Journal of Pharmacology and Experimental Therapeutics; (USA), Vol. 251:3; ISSN 0022-3565
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ADENOSINE
RECEPTORS
CHEMICAL COMPOSITION
AFFINITY
BIOCHEMICAL REACTION KINETICS
BRAIN
CELL MEMBRANES
IN VITRO
INHIBITION
LIGANDS
RADIOASSAY
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMALS
BODY
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANS
PROTEINS
REACTION KINETICS
RIBOSIDES
RODENTS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques