On the basis of sex: male vs. female rat adenosine A1/A2A receptor affinity

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Abstract Objective To ensure reproducibility in biomedical research, the biological variable sex must be reported; yet a reason for using male (instead of female) rodents is seldom given. In our search for novel adenosine receptor ligands, our research group routinely determines a test compound’s binding affinities at male Sprague-Dawley rat (r) adenosine A 1 and A 2A receptors via in vitro radioligand binding studies. This pilot study compared the binding affinities of four adenosine receptor ligands (frequently used as reference standards) at male and female adenosine rA 1 and rA 2A receptors. Results The inhibition constant ( K i ) values determined using female rats correspond well to the values obtained using male rats and no markable difference could be observed in affinity and selectivity of reference standards. For example, DPCPX the selective adenosine A 1 receptor antagonist: male rA 1 K i : 0.5 ± 0.1 nM versus female rA 1 K i : 0.5 ± 0.03 nM; male rA 2A K i : 149 ± 23 nM versus female rA 2A K i : 135 ± 29 nM. From the limited data at hand, we conclude that even when using female rats for in vitro studies without regard for the oestrous cycle, the obtained data did not vary much from their male counterparts.

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