Role of G-proteins and adenylate cyclase in antinociception produced by intrathecal purines.
The effects of pertussis toxin, forskolin and phosphodiesterase inhibitors on the antinociceptive action of intrathecal purines were examined to investigate the possible involvement of adenylate cyclase in spinal antinociception. Pretreatment with pertussis toxin (0.25 and 0.5 microgram) inhibited the antinociceptive action of L-phenyl-isopropyladenosine (L-PIA), N6-cyclohexyladenosine (CHA) and 5'-N-ethylcarboxamide adenosine (NECA) in the tail flick and hot plate tests. Forskolin (10-30 micrograms) reduced the effect of CHA and NECA in the hot plate test. Ro 201724 (30 micrograms) and Rolipram (20 micrograms) inhibited CHA in the tail flick and hot plate tests, but did not affect NECA in either test. These results suggest (1) spinal antinociception by purines is mediated by interactions with G-proteins (Gi linked to adenylate cyclase and/or Go linked to ion channels) (2) spinal antinociception by CHA is due to inhibition of adenylate cyclase (3) a separate mechanism, which does not involve stimulation of adenylate cyclase, may be involved in the spinal action of NECA.
Sawynok
J
J
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Reid
A
A
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000502:physiology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D007278:Injections, Spinal; D008297:Male; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D037342:Pertussis Toxin; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011687:Purines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000700:Analgesics; D010726:Phosphodiesterase Inhibitors; D011687:Purines; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases