Abstract
While the concept of a receptor reserve (spare receptors) is old, their presence on human cells as an adaptive mechanism in cardiovascular disease is a new suggestion. The presence of spare receptors is suspected when the activation of a weak fraction of receptors leads to maximal biological effects, in other words, when the half-maximal effective concentration (EC50) for a biological effect (cAMP production, for example) is lower than the affinity (KD) of the ligand for a receptor. Adenosine is an ATP derivative that strongly impacts the cardiovascular system via its four membrane receptors, named A1R, A2AR, A2BR, and A3R, with the A1R being more particularly involved in heart rhythm, while the A2AR controls vasodilation. After a general description of the tools necessary to explore the presence of spare receptors, this review focuses on the consequences of the presence of spare adenosine receptors in cardiovascular physiopathology. Finally, the role of the adenosinergic system in the long-term potentiation and its possible consequences on the physiopathology are also mentioned.
Highlights
Clark’s receptor theory [1] describes the relationship between a ligand and its receptor as a linear response, suggesting that the maximal receptor response to a drug or an endogenous ligand is equal to the maximal tissue response
Three distinct processes have been proposed that characterize ligand–receptor interaction: (i) receptor binding, defined by the equilibrium dissociation constant (KD), used to determine affinity; (ii) receptor activation that introduces the notion of efficiency; and (iii) post-activation transduction signal that is mostly characterized by a signal amplification [5]
From a pharmacological point of view, the presence of spare receptors for an agonist is suspected when maximal or near-activation occurs during partial occupation of the receptors [14], in other words, when the maximal biological effect is obtained at a lower agonist concentration than that required for the occupancy of all the receptors (Bmax)
Summary
Clark’s receptor theory [1] describes the relationship between a ligand and its receptor as a linear response, suggesting that the maximal receptor response to a drug or an endogenous ligand is equal to the maximal tissue response. From a pharmacological point of view, the presence of spare receptors for an agonist is suspected when maximal or near-activation occurs during partial occupation of the receptors [14], in other words, when the maximal biological effect (assessed, for example, by the cAMP production) is obtained at a lower agonist concentration than that required for the occupancy of all the receptors (Bmax). The presence of a receptor reserve is suspected when the half-maximal biological effect value (EC50) is lower than the agonist affinity constant for the receptor (KD). This can be assessed by a low EC50/KD ratio [9,15]. As a result of signal amplification, epinephrine at a concentration as low as 10−10 M promotes liver glycogenolysis via the cAMP production in the range of 10−6 M (suggesting a 10,000-fold amplification) and releases sufficient physiological glucose in blood [18]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call