Enprofylline and Theophylline on Small Human Placental Arteries: Studies of in Vitro Effects and Mode of Action

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Abstract
Vascular effects of theophylline and enprofylline, a novel xanthine derivative lacking adenosine receptor antagonism, were studied comparatively in tubular preparations of small human placental arteries mounted in an isometric myograph. Both xanthines produced concentration-dependent (10−7-3 × 10−3 M) relaxation of arteries contracted by PGF2α or PGE2 in both normal Ca2+-medium and in Ca2+-depleted medium. Enprofylline was about three times more potent than theophylline. Also in vasopressin-contracted arteries enprofylline was a more potent vasodilator in both media. In contrast the xanthines were equally potent in relaxation of the tonic as well as the phasic part of a K+-induced contraction, but less potent than in relaxation of PG-induced contractions. Propranolol, phentolamine, atropine, indomethacin or tetrodotoxin did not influence the xanthine relaxations. It is concluded that the theophylline-induced relaxation of small human placental arteries is not due to adenosine receptor antagonism. A common important mechanism of action, in which enprofylline is more potent than theophylline, seems to be interference with intracellular Ca2+-binding/mobilisation processes. Some decrease in cellmembrane Ca2+-permeability produced by the xanthines seems to take part in the mechanism of relaxation.