Pertussis toxin modifies the effect of central morphine on rat intestinal motility.
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.
Parolaro
D
D
Institute of Pharmacology, Faculty of Sciences, University of Milan, Italy.
Patrini
G
G
Massi
P
P
Parenti
M
M
Rubino
T
T
Giagnoni
G
G
Gori
E
E
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002606:Charcoal; D004594:Electrophysiology; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007276:Injections, Intraventricular; D007422:Intestines / Q000502:physiology; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D037342:Pertussis Toxin; D010761:Phosphorus Radioisotopes; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D010761:Phosphorus Radioisotopes; D011957:Receptors, Opioid; D010566:Virulence Factors, Bordetella; D002606:Charcoal; D000244:Adenosine Diphosphate; D009020:Morphine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins