Bradykinin-induced stimulation of afferent fibres is mediated through protein kinase C.
In an in vitro preparation of the neonatal spinal cord with the tail attached, brief administration of bradykinin or capsaicin in the tail superfusate containing a normal calcium concentration, activated peripheral fibres and produced a depolarization recorded at a spinal ventral root (L3-L5). Perfusion with a phorbol ester (4 beta-phorbol 12,13-dibutyrate, PDBu) produced a small and inconsistent activation of peripheral fibres. In subsequent experiments calcium was omitted from the tail superfusate since under this condition responses to bradykinin and capsaicin were unchanged but PDBu evoked reproducible depolarization when applied at intervals of 60 min or more. Prolonged desensitization followed repeated administration at shorter intervals. Pretreatment of the tail with capsaicin, to impair transmission in C-fibres, abolished the effect of each agonist. Inactivation of protein kinase C with the inhibitor staurosporine (10-100 nM) attenuated the effect of bradykinin and PDBu but not that of capsaicin. Pretreatment with PDBu also attenuated the effect of bradykinin. These data suggest that a phorbol ester and bradykinin stimulate capsaicin-sensitive C-fibres by a mechanism which involves the activation of protein kinase C.
Dray
A
A
Sandoz Institute for Medical Research, London, U.K.
Bettaney
J
J
Forster
P
P
Perkins
M N
MN
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D019311:Staurosporine
D000470:Alkaloids; D004791:Enzyme Inhibitors; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D019311:Staurosporine; D002211:Capsaicin; D001920:Bradykinin