Involvement of the nitric oxide-cyclic GMP pathway in the desensitization of bradykinin responses of cultured rat sensory neurons.
Bradykinin (BK) excites a subset of dorsal root ganglion neurons by inducing an inward cation current (IBK) that strongly desensitizes and is accompanied by elevations in cGMP. We have examined the links between cGMP metabolism and IBK. The BK dose dependencies of IBK activation, desensitization, and cGMP production are comparable. Stimulation (with sodium nitroprusside [NP] or 8-bromo-cGMP [8Br-cGMP]) or inhibition (with methylene blue, hemoglobin, and nitric oxide synthase [NOS] inhibitors) of cGMP levels did not mimic or diminish IBK. However, desensitization was affected by the following agents: first, desensitization was enhanced by NP and reduced by NOS inhibitors. Second, the effects of NOS inhibitors could be overcome by 8Br-cGMP or L-arginine. Third, 8Br-cGMP modification of desensitization required receptor occupancy. We conclude that the NO-cGMP pathway affects a component of IBK desensitization at the receptor or G protein level.
McGehee
D S
DS
Department of Physiology, University of North Carolina, Chapel Hill 27599.
Goy
M F
MF
Oxford
G S
GS
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004361:Drug Tolerance; D004553:Electric Conductivity; D005727:Ganglia, Spinal / Q000166:cytology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D019323:omega-N-Methylarginine
D009599:Nitroprusside; D019335:Nitroarginine; D015124:8-Bromo Cyclic Adenosine Monophosphate; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D006152:Cyclic GMP; D001920:Bradykinin