Modification of morphine-induced analgesia and toxicity by pertussis toxin.
The present study evaluates the effect of pertussis toxin (PTX) on morphine-induced analgesia and lethality. Mice were injected with 0.2 microgram PTX intracerebroventricularly (i.c.v.) and 0.2 micrograms PTX intrathecally (i.t.) or saline. Mice were tested for morphine-induced analgesia (tail flick) and lethality 16 days later; mice were also examined for pentobarbital-induced mortality. Morphine analgesic potency was decreased by approximately 4-fold in PTX-treated mice compared to controls. Conversely, the lethal potency of morphine was increased by 10-fold in PTX-treated mice compared to controls. PTX treatment did not alter the lethal potency of pentobarbital. Morphine-induced analgesia and lethality were dose-dependently antagonized by naloxone in both PTX and saline-treated groups. The results of this study suggest that morphine analgesia is mediated through PTX-sensitive G proteins. On the other hand, morphine-induced lethality appears to be limited by PTX-sensitive factor(s) since PTX treatment enhanced morphine's lethal potency. The increase in lethal potency of morphine may be due to unmasking of an excitatory opioid receptor mediated effect by PTX.
Lutfy
K
K
College of Pharmacy and Allied Health Professions, St. John's University, Queens, NY 11439.
Chang
S C
SC
Candido
J
J
Jang
Y
Y
Sierra
V
V
Yoburn
B C
BC
D000698:Analgesia; D000818:Animals; D008297:Male; D051379:Mice; D009020:Morphine; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D010566:Virulence Factors, Bordetella; D009020:Morphine; D037342:Pertussis Toxin