# The interaction of AB-680, a CD73 inhibitor, with NBTI, a nucleoside transporter inhibitor, on the adenosinergic control of atrial contractility

## TL;DR

This study explores how a CD73 inhibitor interacts with a nucleoside transporter inhibitor to affect adenosine levels and atrial contractility in guinea pig hearts.

## Contribution

The study introduces a novel method to assess interstitial adenosine concentration changes using receptorial responsiveness in an isolated atrial model.

## Key findings

- AB-680 partially reversed the adenosine-elevating effect of NBTI in isolated guinea pig atria.
- DMSO had less interference in measurements compared to the in vivo-recommended buffer.
- AB-680 reduced the equieffective CPA concentration by at least half when co-administered with NBTI in DMSO.

## Abstract

In this study, we investigated the influence of AB-680, a highly potent CD73 inhibitor, on the effect of NBTI, a nucleoside transport blocker, exerted on concentration-effect (E/c) curves generated with CPA, a relatively stable, selective A1 adenosine receptor full agonist, in isolated, paced guinea pig left atria.

Transformations of the CPA E/c curves, constructed in the absence and presence of AB-680 and NBTI (in all combinations), were used to assess the changes in the interstitial adenosine concentration. These changes were quantified with the receptorial responsiveness method (RRM), a unique procedure providing the CPA concentration (as cx), which is equieffective with the increase in the interstitial adenosine concentration caused by NBTI. AB-680 and NBTI were dissolved in DMSO (recommended for in vitro use) as well as in a buffer (recommended for in vivo use), and the results were compared.

We found that AB-680, when added alone, did not affect the response to CPA. In turn, AB-680, when administered together with NBTI, was able to partially reverse the elevating effect of NBTI on the interstitial adenosine level. Nevertheless, the inhibitory action of AB-680 on the effect of NBTI appeared to be smaller than that of PSB-12379, another CD73 inhibitor investigated earlier in the same experimental model. We also found that DMSO interfered with our measurements to a lesser extent than the buffer recommended for in vivo studies. In addition, AB-680, when co-administered with NBTI (both dissolved in DMSO), reduced cx (i.e. probably also the surplus interstitial adenosine) by at least half.