Nicotine-induced antinociception in mice: role of G-proteins and adenylate cyclase.
The effects of pertussis toxin, forskolin, and cAMP analogues on the antinociceptive action of nicotine were examined to investigate the possible involvement of adenylate cyclase and G-proteins in nicotine's antinociceptive effect. Intrathecal injection of pertussis toxin (0.25 and 0.50 micrograms) in mice inhibited nicotine-induced antinociception in the tail-flick test. The effect of the toxin was dose and time dependent. Forskolin, a potent adenylate cyclase activator, and 8-(-4-chlorophenylthio) adenosine-3':5' monophosphate, cyclic (8-CPT-cAMP), a cAMP analogue, inhibited the antinociceptive effects of nicotine in a dose-dependent manner. EGTA reversal of 8-CPT-cAMP's inhibitory effects suggests that calcium may to be involved. These data implicate the possible involvement of a G-protein and a second messenger system (activation of a cAMP-dependent protein kinase and increase in cyclic AMP levels) in nicotine-induced analgesia in mice.
Damaj
M I
MI
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613.
Welch
S P
SP
Martin
B R
BR
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000502:physiology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology*; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D037342:Pertussis Toxin; D011930:Reaction Time / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000700:Analgesics; D006584:Hexamethonium Compounds; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D003994:Bucladesine; D008464:Mecamylamine; D009538:Nicotine; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D002118:Calcium