Abstract
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.
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