Effects of intrathecal or intracerebroventricular pretreatment with pertussis toxin on antinociception induced by beta-endorphin or morphine administered intracerebroventricularly in mice.
We have previously demonstrated that beta-endorphin and morphine, when administered supraspinally, produce antinociception by activating different descending pain inhibitory systems in both rats and mice. However, the signal transduction mechanisms involved in the descending pain-inhibitory systems that are activated by beta-endorphin and morphine administered intracerebroventricularly (i.c.v.) have not been characterized. Therefore, in the present study, the effects of intrathecal (i.t.) and i.c.v. pretreatments with pertussis toxin (PTX) on antinociception induced by beta-endorphin or by morphine administered i.c.v. were studied in ICR mice. Antinociception was assessed by the tail-flick assay and by the hot-plate assay. Intrathecal pretreatment with PTX (0.5 microgram) for 6 days effectively reduced the inhibition of the tail-flick response induced by beta-endorphin (1 microgram) or by morphine (1 microgram) administered i.c.v. However, i.t. pretreatment with PTX was not effective in reducing the inhibition of the hot-plate response induced by beta-endorphin or by morphine administered i.c.v. Intracerebroventricular pretreatment with PTX (0.5 microgram) for 6 days effectively reduced the inhibition of the tail-flick and hot-plate responses induced by morphine (1 microgram), but not that induced by beta-endorphin (1 microgram), administered i.c.v. Our results suggest that there are PTX-sensitive G proteins coupled to the spinal descending pain inhibitory systems that are activated by beta-endorphin and morphine administered i.c.v. At a supraspinal level, i.c.v. morphine- but not beta-endorphin-induced antinociception is mediated by PTX-sensitive G proteins.
Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Suwon, Kyungki-Do, Korea.
K M
KM
Chung
D K
DK
Song
H W
HW
Suh
M H
MH
Lee
Y H
YH
Kim
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D019204:GTP-Binding Proteins / Q000378:metabolism; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella / Q000008:administration & dosage / Q000494:pharmacology*; D001615:beta-Endorphin / Q000008:administration & dosage / Q000494:pharmacology*
D000700:Analgesics; D010566:Virulence Factors, Bordetella; D001615:beta-Endorphin; D009020:Morphine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins