Differential interactions of cholecystokinin and FLFQPQRF-NH2 with mu and delta opioid antinociception in the rat spinal cord.
An in vivo preparation of the rat spinal cord was used to investigate the electrophysiological actions of two non-opioid peptides, cholecystokinin (CCK8) and FLFQPQRF-NH2 (FMRFamide-like peptide) applied intrathecally. These compounds were examined alone and as a pretreatment before DAGO, a mu opioid agonist, and DSTBULET, a delta opioid agonist, both which selectively reduce C-fibre evoked dorsal horn neurone activity elicited by transcutaneous electrical stimulation. Given alone, CCK8 (1 microgram) elicited a modest enhancement of C-fibre induced activity which returned to control levels after 20 min, while FLFQPQRF-NH2 (10 micrograms) had no significant effect on C-fibre evoked firing. As a pretreatment, however, both peptides selectively prevented the inhibition of C-fibre evoked activity normally resulting from intrathecal DAGO, while having no effect on that resulting from DSTBULET. Further, CCK8 enhanced the facilitation of C-fibre evoked firing normally observed with low doses of DAGO. These data indicate that the anti-opioid roles suggested for CCK8 and FLFQPQRF-NH2 may be specific for neural elements utilizing the mu opioid receptor.
Magnuson
D S
DS
Department of Pharmacology, University College, London.
Sullivan
A F
AF
Simonnet
G
G
Roques
B P
BP
Dickenson
A H
AH
D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects; D007278:Injections, Spinal; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D012844:Sincalide / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology
D004745:Enkephalins; D009842:Oligopeptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C054868:tyrosyl-seryl(O-tert-butyl)-glycyl-phenylalanyl-leucyl-threonine; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; D012844:Sincalide