Related Experiment Videos
Pertussis toxin modifies the effect of central morphine on rat intestinal motility
D Parolaro1, G Patrini, P Massi
1Institute of Pharmacology, Faculty of Sciences, University of Milan, Italy.
Abstract:
To find whether the antipropulsive effect of morphine administered intracerebroventricularly (i.c.v.) depends on a G-protein-mediated mechanism, we studied the effect of i.c.v. pertussis toxin (PTX) pretreatment on morphine-induced inhibition of intestinal motility. The influence of PTX was evaluated on intestinal transit (charcoal meal test) and by monitoring of intestinal myoelectrical activity. The antitransit effect of morphine (10 micrograms/rat) was antagonized by about 70% 3, 6, 9 and 12 days after PTX pretreatment (1 microgram/rat) and it was partially restored after 25 days. I.c.v. morphine abolished the regular appearance of the myoelectric migrating complex (MMC) recorded in the rat jejunum and this effect was completely antagonized by PTX pretreatment. When morphine was injected 25 days after PTX, it significantly reduced MMC frequency, confirming the partial recovery seen in the transit experiments. The pertussis toxin-catalyzed ADP ribosylation of a 39-41 kDa substrate in membranes prepared from hypothalamus and midbrain of rats injected with toxin 6 days before was strongly reduced as compared to the controls. On the contrary, after 25 days, ADP ribosylation was the same in treated and control rats. Thus the antipropulsive effect of central morphine could be initiated at receptor sites which interact with G-protein substrates of pertussis toxin.
Insights
Central morphine
Area of Science:
- Neuropharmacology
- Gastroenterology
- Molecular Biology
Background:
- Opioid receptors are known to influence gastrointestinal motility.
- The role of G-protein signaling in central opioid effects on the gut is not fully understood.
Purpose of the Study:
- To investigate if the G-protein-mediated mechanism is involved in the antipropulsive effect of intracerebroventricularly administered morphine.
- To elucidate the involvement of pertussis toxin-sensitive G-proteins in morphine's action on intestinal motility.
Main Methods:
- Intracerebroventricular (i.c.v.) administration of pertussis toxin (PTX) in rats.
- Assessment of intestinal transit using a charcoal meal test.
- Monitoring of intestinal myoelectrical activity, specifically the myoelectric migrating complex (MMC).
- Evaluation of PTX-catalyzed ADP ribosylation of specific substrates in rat brain membranes.
Main Results:
- PTX pretreatment significantly antagonized morphine's antitransit effect and its abolition of MMC.
- These effects were observed between 3 and 12 days post-PTX, with partial recovery after 25 days.
- PTX reduced ADP ribosylation of a 39-41 kDa substrate, indicating G-protein involvement, which diminished by day 25.
Conclusions:
- The antipropulsive effect of central morphine is initiated at receptor sites coupled to G-protein substrates sensitive to pertussis toxin.
- G-protein-mediated signaling pathways are crucial for morphine's inhibitory action on intestinal motility.