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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.
Insights
Tetracyclines inhibit muscle contractions by reducing acetylcholine release, primarily through the release of endogenous opioids. This action was observed in guinea-pig ileum preparations.
Area of Science:
- Pharmacology
- Neurogastroenterology
- Muscle Physiology
Background:
- Tetracyclines are known for their antibiotic properties.
- Their non-antibiotic effects on the nervous system are less understood.
- The myenteric plexus controls gastrointestinal motility.
Purpose of the Study:
- To investigate the inhibitory effects of tetracyclines on guinea-pig ileum muscle contractions.
- To elucidate the mechanism of action of tetracyclines on neurotransmitter release.
- To determine the role of endogenous opioids in tetracycline-induced inhibition.
Main Methods:
- Using isolated guinea-pig ileum preparations with intact myenteric plexus.
- Electrical field stimulation to induce twitch responses.
- Measuring acetylcholine release.
- Pharmacological manipulation with ganglion blockers, antagonists, and peptidase inhibitors.
Main Results:
- Tetracycline, chlortetracycline, minocycline, and doxycycline inhibited twitch responses in a concentration-dependent manner.
- These tetracyclines reduced presynaptic acetylcholine release.
- The inhibitory effect was partially reversed by naloxone, suggesting opioid involvement.
- Inhibition was enhanced by peptidase inhibitors, further supporting opioid mediation.
Conclusions:
- Certain tetracyclines exert an inhibitory effect on gastrointestinal motility.
- This inhibition is mediated by presynaptic reduction of acetylcholine release.
- The mechanism involves the release of endogenous opioids from the myenteric plexus.