Cardiac functional responses to adenosine by PD 81,723, an allosteric enhancer of the adenosine A1 receptor
Mudumbi, R.V.; Montamat, S.C.; Bruns, R.F.; Vestal, R.E.
American Journal of Physiology 264(3 Pt 2): H1017-H1022
1993
ISSN/ISBN: 0002-9513 PMID: 8456969 Document Number: 422342
Adenosine, a locally released and rapidly metabolized nucleoside, protects the heart from damage during ischemia by reducing oxygen demand and increasing oxygen supply. The aminothiophene derivative (2-amino-4,5-dimethylthien-3-yl)(3-(trifluoromethyl)phenyl)methanone (PD 81,723) has been shown to act as an allosteric enhancer of the adenosine A-1 receptor in brain membranes and thyroid cells. The present study investigates the effects of PD 81,723 in spontaneously contracting right atria and electrically stimulated left atria isolated from Sprague-Dawley rats. N-6-cyclopentyladenosine (CPA), an adenosine A-1 receptor agonist, produced concentration-dependent inhibition of heart rate in right atria and contractile parameters in left atria. In the right atrium, 5 mu-M of PD 81,723 significantly shifted the concentration-response curves for CPA to the left, both in the absence and presence of a nonselective adenosine receptor antagonist, 8-(p-sulfophenyl)theophylline (8-SPT, 10 mu-M). In the left atrium, PD 81,723 also shifted the concentration-response curves for CPA to the left, but only in the presence of 8-SPT. Potentiation of CPA-induced negative chronotropic and inotropic responses with PD 81,723, although not significant, was also observed in the presence of a selective adenosine A-1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 1 nM). These results demonstrate that PD 81,723 enhances the direct negative chronotropic and inotropic effects of adenosine A-1 receptor activation in rat atria.