title: An inhibitory action of tetracyclines on guinea-pig myenteric plexus.
abstract: In plexus containing preparations of the longitudinal muscle of the guinea-pig ileum, an inhibitory action of tetracyclines on twitch-responses to electrical field stimulation was found. Tetracycline, chlortetracycline, minocycline and doxycycline, but not oxytetracycline (0.02 to 1.6 mmol/l) caused a concentration-dependent presynaptic inhibition of acetylcholine release. The inhibitory effect of the tetracyclines was also obtained after ganglion block by hexamethonium (30 mumol/l). The inhibitory effect of the tetracyclines was not antagonized by piperoxan (2 mumol/l) or yohimbine (1 mumol/l) and was partly reduced by the presence of naloxone (1 to 50 nmol/l). After exposing the preparation the peptidase inhibitors, i.e., to the combination of bestatin (10 mumol/l), captopril (10 mumol/l) and thiorphan (0.3 mumol/l), the inhibitory effect of tetracyclines was significantly increased. From these results it would appear that twitch-inhibition caused by tetracycline, chlortetracycline, minocycline and doxycycline is mainly mediated via the release of endogenous opioids from the myenteric plexus.
mesh_terms: D000818:Animals; D002216:Captopril / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009197:Myenteric Plexus / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D013754:Tetracyclines / Q000494:pharmacology*; D015244:Thiorphan; D008625:Tiopronin / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D011480:Protease Inhibitors; D013754:Tetracyclines; D009270:Naloxone; D002216:Captopril; D015244:Thiorphan; D008625:Tiopronin; D007930:Leucine; C012211:ubenimex