Characterization of [3H]-N-[R-(2- Benzothiazolyl)thio-2-propyl]-2-chloroadenosine ([3H]-NNC 21-0136) binding to rat brain: Profile of a novel selective agonist for adenosine A1 receptors

✍ Scribed by Christian Thomsen; Jacob S. Valsborg; Christian Foged; Lars Knutsen

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 389 KB
• Volume: 42
• Category: Article
• ISSN: 0272-4391
• DOI: 10.1002/(sici)1098-2299(199710)42:2<86::aid-ddr5>3.0.co;2-l

✦ Synopsis

thio-2-propyl]-2-chloroadenosine (NNC 21-0136) is a novel adenosine agonist with neuroprotectant properties in rodent models of focal and global ischemia that exhibits diminished cardiovascular side effects when compared to reference A 1 agonists [Sheardown et al., 1995]. NNC 21-0136 is shown to be a potent agonist of adenosine A 1 receptors showing around 60-and 30-fold selectivity over adenosine A 2A and A 3 receptors, respectively. In order to further characterize the central nervous system molecular target for NNC 21-0136, the compound has been radiolabeled and utilized in receptor binding experiments. In vitro receptor autoradiography with [ 3 H]-NNC 21-0136 revealed high levels of receptors in the CA1 region of the hippocampus, the granule cell layer of the cerebellar cortex, and moderate uniform levels throughout the cerebral cortex. [ 3 H]-NNC 21-0136 binding to rat cerebral cortical membranes was reversible and saturable (B max = 0.98 ± 0.04 pmol/mg protein) to a high affinity site (K d = 1.16 ± 0.06 nM) as determined by saturation binding experiments. [ 3 H]-NNC 21-0136 binding was sensitive to guanosine-5´-O-(3-thio)triphosphate-γ-S and enhanced by the presence of divalent cations (Ca 2+ and Mg 2+ ). A highly significant correlation between the affinities of several compounds to displace [ 3 H]-NNC 21-0136 binding as compared to [ 3 H]-N-R-(2-phenylisopropyl)adenosine ([ 3 H]-R-PIA) binding to adenosine A 1 receptors in rat cortical membranes was observed. We conclude that [ 3 H]-NNC 21-0136 is a new, selective radioligand for adenosine A 1 receptors.