Enprofylline and theophylline on small human placental arteries: studies of in vitro effects and mode of action.
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 X 10(-3) M) relaxation of arteries contracted by PGF2 alpha 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.
D001158:Arteries / Q000187:drug effects; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D010920:Placenta / Q000098:blood supply*; D011188:Potassium / Q000494:pharmacology; D011247:Pregnancy; D011453:Prostaglandins / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014970:Xanthines / Q000494:pharmacology*
D001993:Bronchodilator Agents; D011453:Prostaglandins; D014970:Xanthines; D013806:Theophylline; C034347:enprofylline; D011188:Potassium; D002118:Calcium