Bradykinin enhances excitability in cultured rat sensory neurones by a GTP-dependent mechanism.
The excitatory action of bradykinin (Bk; 0.1-1.0 microM) on cultured rat dorsal root ganglion neurones (DRGs) was studied using the whole cell clamp technique. In a subpopulation of DRGs, a 1 s depolarising voltage pulse from -70 to +20 mV evoked more than one inward current. In these neurones, local application of Bk increased the inward current frequency from 7.0 +/- 0.7 s-1 to 14.9 +/- 1.0 s-1 (mean +/- S.E.M., n = 53). Intracellular application of the GTP analogue, guanosine 5'O-3-thiotriphosphate (GTP gamma S) mimicked this excitatory action of Bk: the frequency of inward currents increased from 5.0 +/- 0.8 s-1, 30 s after the start of recording to 6.9 +/- 1.1 s-1 at 5 min to a maximum of 18.5 +/- 2.2 s-1 at 15 min (n = 16). In control cells, the frequency decreased from 4.6 +/- 0.8 s-1 to 2.5 +/- 0.5 s-1 at 5 min (n = 12). Bk also increased excitability in 4/11 Herpes Simplex Virus I (HSV-I)-infected DRGs. Thus, we demonstrate an excitatory action of Bk in DRGs, which may involve G-protein activation.
McGuirk
S M
SM
Department of Pharmacology, St. George's Hospital Medical School, London, U.K.
Vallis
Y
Y
Pasternak
C A
CA
Dolphin
A C
AC
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002478:Cells, Cultured; D004558:Electric Stimulation; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D013873:Thionucleotides / Q000494:pharmacology*
D013873:Thionucleotides; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D001920:Bradykinin