CCPA (biochemistry)

Template:Chembox image cellTemplate:Chembox AllOtherNamesTemplate:Chembox headerbarTemplate:Chembox IndexlistTemplate:Chembox JmolTemplate:Chembox ChEMBLTemplate:Chembox ECHATemplate:Chembox E numberTemplate:Chembox IUPHAR ligandTemplate:Chembox UNIITemplate:Chembox CompToxTemplate:Chembox headerbarTemplate:Chembox HazardsTemplate:Chembox Datapage checkTemplate:Yesno

CCPA

Template:Longitem	Template:Unbulleted list
Abbreviations	CCPA
ChEBI	Template:Unbulleted list
ChemSpider	Template:Unbulleted list
DrugBank	Template:Unbulleted list
EC Number	Template:Unbulleted list
KEGG	Template:Unbulleted list
MeSH	2-chloro-N(6)cyclopentyladenosine
Template:Longitem	Template:Unbulleted list
RTECS number	Template:Unbulleted list
Template:Longitem	C15H20ClN5O4
Molar mass	369.80 g/mol

2-Chloro-N⁶-cyclopentyladenosine (CCPA) is a specific receptor agonist for the Adenosine A1 receptor. It is similar to N⁶-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 [³H]CCPA 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 N⁶ position of the adenosine molecule. These modifications enhance its receptor selectivity and binding affinity. The molecular formula of CCPA is C₁₅H₁₉ClN₅O₄, with a molecular weight of approximately 367.80 g/mol.

Pharmacological Profile

Affinity and Selectivity for Adenosine Receptors

CCPA exhibits a high binding affinity for A₁ 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 A₁ over A_2A.

Functional Effects

As an A₁ receptor agonist, CCPA effectively inhibits adenylate cyclase activity. In rat adipocyte membranes, it achieved an IC₅₀ 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 A₁ receptors, it functions as a moderate antagonist at human A₃ adenosine receptors. Studies using Chinese hamster ovary cells expressing human A₃ 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 A₃ 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 A₁ receptor-mediated cardioprotective mechanisms, including modulation of heart rate and ischemic responses (Ischemia). In neurological contexts, CCPA aids in elucidating the role of A₁ receptors in neurotransmission and neuroprotection. Additionally, its antagonistic properties at A₃ receptors provide insights into the complex interplay between different adenosine receptor subtypes.

2-Chloro-N⁶-cyclopentyladenosine (CCPA) stands out as a potent and selective adenosine A₁ receptor agonist with unique antagonistic effects on A₃ 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

Template:Adenosinergics