Theophylline effects on phasic tension and slow inward current of isolated frog atrial fibres: influence on the action of isoprenaline.
The action of theophylline on phasic tension and slow inward current (Isi) was investigated on isolated voltaged-clamped frog atrial fibres. The action of theophylline was both dose- and time-dependent; the most effective dose was 2.10(-3)M. Theophylline induced a rapid positive inotropic effect which cannot be attributed to a beta-adrenoceptor stimulation or to an adenosine antagonism; this effect was closely related to an increase in slow inward current (Isi), probably due to an inhibition of phosphodiesterase activity and a subsequent increase in cAMP content. The decline of the positive inotropic effect of theophylline was discussed in terms of additional effects of the drug. Theophylline, consistently with its phosphodiesterase inhibitory action, was shown to potentiate the effects of isoprenaline on phasic tension and Isi; however no potentiation was observed after reserpine-induced depletion of endogenous catecholamines. It might be thought that non-specific effects of reserpine on some steps of cardiac excitation-contraction coupling counteract the effects of theophylline.
Gauthier
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C
Laboratory of General Physiology, CNRS URA 290 Biomembranes, University of Poitiers, France.
Soustre
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H
D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D004357:Drug Synergism; D006325:Heart Atria / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology; D011893:Rana esculenta; D011895:Rana ridibunda; D012110:Reserpine / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology*
D012110:Reserpine; D011433:Propranolol; D013806:Theophylline; C028322:8-phenyltheophylline; D000243:Adenosine Deaminase; D007545:Isoproterenol