Characterization of the K(+)-channel-coupled adenosine receptor in
guinea pig atria
Naunyn Schmiedebergs Arch Pharmacol, 340 (6):
684-8 (December 1989)Tawfik-Schlieper, H Klotz, K N Kreye, V A Schwabe, U In Vitro Research
Support, Non-U.S. Gov't Germany, west Naunyn-Schmiedeberg's archives
of pharmacology Naunyn Schmiedebergs Arch Pharmacol. 1989 Dec;340(6):684-8..Abstract
In the present work we studied the pharmacological profile of adenosine
receptors in guinea pig atria by investigating the effect of different
adenosine analogues on 86Rb(+)-efflux from isolated left atria and
on binding of the antagonist radioligand 8-cyclopentyl-1,3-3Hdipropylxanthine
( 3HDPCPX) to atrial membrane preparations. The rate of 86Rb(+)-efflux
was increased twofold by the maximally effective concentrations of
adenosine receptor agonists. The EC50-values for 2-chloro-N6-cyclopentyladenosine
(CCPA), R-N6-phenylisopropyladenosine (R-PIA), 5'-N-ethylcarboxamidosadenosine
(NECA), and S-N6-phenylisopropyladenosine (S-PIA) were 0.10, 0.14,
0.24 and 12.9 microM, respectively. DPCPX shifted the R-PIA concentration-response
curve to the right in a concentration-dependent manner with a KB-value
of 8.1 nM, indicating competitive antagonism. 3HDPCPX showed a
saturable binding to atrial membranes with a Bmax-value of 227 fmol/mg
protein and a KD-value of 1.3 nM. Competition experiments showed
a similar potency for the three agonists CCPA, R-PIA and NECA. S-PIA
is 200 times less potent than R-PIA. Our results suggest that the
K+ channel-coupled adenosine receptor in guinea pig atria is of an
A1 subtype.