Effects of 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a highly selective adenosine receptor antagonist, on force of contraction in guinea-pig atrial and ventricular cardiac preparations.
The effects of the A1 adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) on force of contraction were examined in isolated electrically driven auricles and papillary muscles from guinea-pigs in the absence and presence of (-)-N6-phenylisopropyladenosine (PIA) and 5'-N-ethylcarboxamidadenosine (NECA). In auricles DPCPX (30-1000 mmol/l) alone increased force of contraction. DPCPX produced only a minor inhibition of phosphodiesterase I-III activity. PIA and NECA alone exerted concentration-dependent negative inotropic effects and the concentration-response curves for PIA and NECA were shifted competitively to the right by the adenosine receptor antagonist DPCPX with similar potency and efficacy. The pA2-value for the inhibition of the effects of PIA and NECA were 9.1 and 8.8, respectively. In papillary muscles DPCPX alone had no inotropic effect. In the presence of isoprenaline PIA and NECA alone exerted concentration-dependent negative inotropic effects and again DPCPX shifted the concentration-response curves for PIA and NECA competitively to the right with similar potency and efficacy. The pA2-value for the inhibition of the effects of PIA and NECA were 9.3 and 9.0, respectively. It is concluded that DPCPX is a potent competitive A1 adenosine receptor antagonist in guinea-pig atrial and ventricular cardiac preparations. Since PIA and NECA were equally potent the cardiac adenosine receptor may constitute a subtype of A1 adenosine receptors differing from the receptor in other tissues such as fat cells. Furthermore, DPCPX has a positive inotropic effect in atrial tissue which cannot be attributed to the A1 receptor antagonism.
von der Leyen
H
H
Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Universität Hamburg, Federal Republic of Germany.
Schmitz
W
W
Scholz
H
H
Scholz
J
J
Lohse
M J
MJ
Schwabe
U
U
D000241:Adenosine / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011983:Receptors, Purinergic / Q000187:drug effects*; D013806:Theophylline / Q000494:pharmacology / Q000031:analogs & derivatives; D014970:Xanthines / Q000494:pharmacology*
D007527:Isoenzymes; D011983:Receptors, Purinergic; D014970:Xanthines; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); C051360:1,3-dipropyl-8-cyclopentylxanthine; D013806:Theophylline; C028322:8-phenyltheophylline; D010727:Phosphoric Diester Hydrolases; D000241:Adenosine