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Contractile response of guinea pig ileum by repetitive application of morphine
T Kusama1, Y Murakoshi, H Murakami
1Department of Physiology and Anatomy, Nihon University College of Pharmacy, Chiba, Japan.
Abstract:
1. The repetitive application of morphine gradually induced a contracture in the isolated guinea pig ileum. 2. The optimum conditions for induction of the contracture were as follows: the concentration, incubation time and washout time of morphine were 1 or 10 microM, 2 and 3 min, respectively. 3. Preincubation with naloxone or TTX blocked this morphine-induced contracture. 4. Among twitch-inhibiting drugs, only clonidine induced a contracture similar to that induced by morphine, while tetrodotoxin (TTX) and adenosine did not. 5. The contracture was also observed in the longitudinal muscle-myenteric plexus preparations. 6. These findings indicate that morphine has a dual inhibitory and excitatory action on the guinea pig ileum and that its repetitive application preferentially diminish the inhibitory one.
Insights
Repeated morphine application causes a contracture in guinea pig ileum, suggesting it diminishes inhibitory effects. This finding is crucial for understanding opioid actions.
Area of Science:
- Pharmacology
- Neuroscience
- Gastrointestinal Physiology
Background:
- Morphine is known for its analgesic properties.
- Opioid receptors are present in the gastrointestinal tract, influencing gut motility.
- The specific mechanisms of morphine's excitatory effects on the ileum are not fully elucidated.
Purpose of the Study:
- To investigate the effects of repetitive morphine application on isolated guinea pig ileum.
- To determine the optimal conditions for inducing morphine-evoked contracture.
- To elucidate the signaling pathways involved in morphine-induced contracture.
Main Methods:
- Isolated guinea pig ileum preparations were used.
- Contractile responses to repetitive morphine application were measured.
- The effects of naloxone and tetrodotoxin (TTX) on morphine-induced contracture were assessed.
- Comparative analysis with other twitch-inhibiting drugs like clonidine, TTX, and adenosine was performed.
Main Results:
- Repetitive morphine application induced a gradual contracture in the guinea pig ileum.
- Optimal conditions for contracture induction involved specific morphine concentrations (1 or 10 microM), incubation time (2 min), and washout time (3 min).
- Preincubation with naloxone or TTX blocked the morphine-induced contracture, indicating involvement of opioid receptors and neuronal pathways.
- Clonidine, but not TTX or adenosine, mimicked the morphine-induced contracture.
- The contracture was also observed in longitudinal muscle-myenteric plexus preparations.
Conclusions:
- Morphine exhibits a dual action (inhibitory and excitatory) on the guinea pig ileum.
- Repetitive morphine application preferentially diminishes the inhibitory effects of morphine.
- These findings contribute to understanding the complex pharmacology of morphine in the enteric nervous system.