Abstract
Radioligand binding to A1 adenosine receptors at brain membranes from
seven species was investigated. The antagonist 8-cyclopentyl-1,3-3Hdipropylxanthine
(3HDPCPX) bound with affinities between 0.17 nM in sheep brain
and 2.1 nM in guinea pig brain. Competition of several antagonists
for 3HDPCPX binding showed that the most potent compounds were
DPCPX with Ki values of 0.05 nM in bovine brain and 1.1 nM in guinea
pig brain and xanthine amine congener (XAC) with Ki 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-N6-3Hcyclopentyl-adenosine
(3HCCPA) were less pronounced, ranging from a KD value of 0.12
nM (hamster brain) to 0.42 nM (guinea pig brain). Agonist competition
for 3HDPCPX binding of photoaffinity labelling, however, exhibited
marked species differences. N-Ethylcarboxamidoadenosine (NECA) and
S-N6-phenylisopropyladenosine (S-PIA) showed 20 to 25-fold different
KD 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
greater than -NECA greater than 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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