Summary
Radioligand binding to A1 adenosine receptors at brain membranes from seven species was investigated. The antagonist 8-cyclopentyl-1,3-[3H]dipropyl-xanthine ([3H]DPCPX) bound with affinities between 0.17 nM in sheep brain and 2.1 nM in guinea pig brain. Competition of several antagonists for [3H]DPCPX binding showed that the most potent compounds were DPCPX with K i values of 0.05 nM in bovine brain and 1.1 nM in guinea pig brain and xanthine amine congener (XAC) with K i values of 0.03 nM in bovine brain and 5.5 nM in guinea pig brain. The differences in affinity of the agonist radioligand 2-chloro-N 6-[3H]cyclopentyl-adenosine ([3H]CCPA) were less pronounced, ranging from a K D value of 0.12 nM (hamster brain) to 0.42 nM (guinea pig brain). Agonist competition for [3H]DPCPX binding of photoaffinity labelling, however, exhibited marked species differences. N-Ethylcarboxamidoa-denosine (NECA) and S-N 6-phenylisopropyladenosine (S-PIA) showed 20 to 25-fold different K D values in different species. NECA had a particularly high affinity in guinea pig brain and was only two-fold less potent than R-PIA. Thus, the difference from the “classical” A1 receptor profile (R-PIA > -NECA > S-PIA) is not sufficient to speculate that A1 receptor subtypes may exist that are coupled to different effector systems. Our data show that these difference can easily be explained by species differences.
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Klotz, KN., Vogt, H. & Tawfik-Schlieper, H. Comparison of A1 adenosine receptors in brain from different species by radioligand binding and photoaffinity labelling. Naunyn-Schmiedeberg's Arch Pharmacol 343, 196–201 (1991). https://doi.org/10.1007/BF00168610
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DOI: https://doi.org/10.1007/BF00168610