2-Chloro-''N''
6-cyclopentyladenosine (CCPA) is a specific
receptor agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agon ...
for the
Adenosine A1 receptor
The adenosine A1 receptor (A1AR) is one member of the adenosine receptor group of G protein-coupled receptors with adenosine as endogenous ligand.
Biochemistry
A1 receptors are implicated in sleep promotion by inhibiting wake-promoting choli ...
. It is similar to
''N''6-cyclopentyladenosine. Initially developed to probe the physiological and pharmacological roles of adenosine receptors, CCPA has become a pivotal tool in cardiovascular and neurological research. Due to CCPA's high affinity for Adenosine A1 receptors, its
tritiated derivative
sup>3HCPA can be used as a
diagnostic tool for detecting the receptors in tissue with low receptor density.
Chemical Structure and Properties
CCPA is chemically characterized by the addition of a
chlorine atom at the 2-position and a
cyclopentyl group at the N
6 position of the
adenosine
Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9- glycosidic bond. Adenosine is one of the four nucleoside build ...
molecule. These modifications enhance its
receptor selectivity and binding affinity. The molecular formula of CCPA is C
15H
19ClN
5O
4, with a molecular weight of approximately 367.80 g/mol.
Pharmacological Profile
Affinity and Selectivity for Adenosine Receptors
CCPA exhibits a high
binding affinity
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from Latin ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usuall ...
for A
1 adenosine receptors. In rat brain membranes, it demonstrated a K
i value of 0.4 nM, indicating potent interaction. Its selectivity is underscored by a significantly lower affinity for A
2A receptors, with a K
i value of 3,900 nM, reflecting nearly 10,000-fold selectivity for A
1 over A
2A.
Functional Effects
As an A
1 receptor
agonist
An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...
, CCPA effectively inhibits
adenylate cyclase activity. In rat
adipocyte
Adipocytes, also known as lipocytes and fat cells, are the cell (biology), cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through ...
membranes, it achieved an IC
50 of 33 nM, demonstrating its potency. Conversely, its influence on A
2A receptors is minimal, requiring much higher concentrations to elicit comparable effects.
Interaction with A3 Adenosine Receptors
Interestingly, while CCPA acts as an agonist at A
1 receptors, it functions as a moderate antagonist at human A
3 adenosine receptors. Studies using Chinese hamster ovary cells expressing human A
3 receptors revealed that CCPA binds with a K
i of 38 nM but does not activate the receptor. Instead, it competitively inhibits the effects of A
3 receptor agonists, highlighting its dual role depending on the receptor subtype.
Applications in Biomedical Research
CCPA's selectivity and efficacy make it an invaluable tool in exploring adenosine receptor functions. In cardiovascular studies, it has been employed to investigate A
1 receptor-mediated cardioprotective mechanisms, including modulation of heart rate and ischemic responses (
Ischemia
Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems ...
). In
neurological
Neurology (from , "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous system, which comprises the brain, the s ...
contexts, CCPA aids in elucidating the role of A
1 receptors in
neurotransmission and
neuroprotection. Additionally, its antagonistic properties at A
3 receptors provide insights into the complex interplay between different adenosine receptor subtypes.
2-Chloro-N
6-cyclopentyladenosine (CCPA) stands out as a potent and selective adenosine A
1 receptor agonist with unique antagonistic effects on A
3 receptors.
Its distinct chemical structure underpins its receptor specificity, rendering it a crucial compound in cardiovascular and neurological research. Ongoing studies continue to uncover its potential therapeutic applications and deepen our understanding of adenosine receptor pharmacology.
References
Nucleosides
Purines
Organochlorides
Adenosine receptor agonists
Cyclopentyl compounds
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