Inhibitory effects of AH 21-132 in guinea-pig isolated ileum and taenia caeci.

摘要: 1. AH 21-132 is being investigated as a potential chemotherapeutic agent for bronchial asthma. The present experiments were designed to determine whether shares the activity of theophylline an antagonist at adenosine A1 receptors and assess its potency relaxant in intestinal smooth muscle. 2. In transmurally-stimulated guinea-pig ileum, (1 mM), but not 10 microM), antagonized twitch depression induced by adenosine. Higher concentrations (100 microM 1 mM) themselves had depressant effect. Neither nor microM) noradrenaline. 3. depressed maximum contractions ileum both acetylcholine (ACh) histamine. 4. treated with hyoscine (greater than caused concentration-dependent log concentration-effect curve potassium chloride. 5. Simultaneous extracellular electrophysiological mechanical recording from taenia caeci showed that microM-1 inhibited spontaneous tension waves their associated bursts electrical spike activity. 6. Intracellular mechano-inhibitory effect mM was accompanied abolition Following abolition, membrane assumed value very close observed during periods quiescence prior drug exposure. 7. cyclic AMP-dependent GMP-dependent phosphodiesterases derived homogenates ileal effective concentration ranges 0.1-1OOO 1-1000 microM, respectively. Theophylline, too, these enzymes each case less potent 21-132. 8. It concluded devoid Al which modulate ACh release intramural cholinergic nerves ileum. At greater IO has on muscle characterized suppression action potentials minor change resting potential. previously been reported depress tone trachealis EC50 lO therefore show this much inhibiting This difference cannot be attributed tissuerelated inhibitor AMP- or GMPdependent phosphodiesterases.