Mechanism of potentiation of contractor responses to catecholamines by methylxanthines in aortic strips.
1. Caffeine and theophylline increased the amplitude of contractor esponses of untreated and reserpine pretreated rabbit aortic strips to catecholamines (adrenaline, alpha-methylnoradrenaline, noradrenaline). Responses to amines without both the 3- and 4-OH groups in the benzene ring (methoxamine, phenylephrine, Synephrine) were not increased by theophylline and only those to Synephrine were slightly enhanced by caffeine.2. Compounds which inhibit catechol-O-methyltransferase (pyrogallol, tropolone, U-0521) potentiated responses to catecholamines and abolished the enhancing effect of theophylline and caffeine. Also, the potentiation produced by inhibitors of O-methylation was significantly reduced in the presence of the methylxanthines.3. Experiments done with the aid of the technique of oil immersion, to eliminate the diffusion of drug from the tissue into the bathing medium, showed that theophylline and caffeine decreased the rate of inactivation of adrenaline by O-methylation.4. These findings indicate that methylxanthines potentiate the contractor responses to catecholamines in aortic strips by inhibiting their extraneuronal inactivation.
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology; D002395:Catecholamines / Q000494:pharmacology*; D003516:Cycloparaffins / Q000494:pharmacology; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology; D066298:In Vitro Techniques; D007659:Ketones / Q000494:pharmacology; D008729:Methoxamine / Q000494:pharmacology; D008745:Methylation; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D009647:Normetanephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011427:Propiophenones / Q000494:pharmacology; D011748:Pyrogallol / Q000494:pharmacology; D011817:Rabbits; D012110:Reserpine / Q000494:pharmacology; D013578:Synephrine / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology*
D002395:Catecholamines; D003516:Cycloparaffins; D007659:Ketones; D011427:Propiophenones; D014970:Xanthines; D011748:Pyrogallol; D009647:Normetanephrine; D010656:Phenylephrine; D002110:Caffeine; D012110:Reserpine; D013806:Theophylline; D008729:Methoxamine; D013578:Synephrine; D009638:Norepinephrine; D004837:Epinephrine