Characterization of the K(+)-channel-coupled adenosine receptor in guinea pig atria

• Published in: Naunyn-Schmiedeberg's archives of pharmacology Vol. 340; no. 6; p. 684
• Main Authors: Tawfik-Schlieper, H, Klotz, K N, Kreye, V A, Schwabe, U
• Format: Journal Article
• Language: English
• Published: Germany 01.12.1989
• Subjects: Adenosine - analogs & derivatives; Adenosine - pharmacology; Animals; Guinea Pigs; In Vitro Techniques; Kinetics; Membranes - metabolism; Myocardium - metabolism; Potassium Channels - metabolism; Receptors, Purinergic - metabolism; Rubidium Radioisotopes; Xanthines
• ISSN: 0028-1298
• DOI: 10.1007/BF00717745

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-[3H]dipropylxanthine [( 3H]DPCPX) 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. [3H]DPCPX 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.