Activation of guanylate cyclase by bradykinin in rat sensory neurones is mediated by calcium influx: possible role of the increase in cyclic GMP.
Bradykinin, which activates polymodal nociceptors, increased cyclic GMP (cGMP) in a capsaicin-sensitive population of cultured sensory neurones from rat dorsal root ganglia (DRG) by stimulating guanylate cyclase, but had no effect on cyclic AMP (cAMP). In nonneuronal cells from DRG, bradykinin increased cAMP, but not cGMP. The bradykinin-induced increase in cGMP in the neurones was completely blocked by removal of extracellular Ca2+, or by incubation of the cells with the calcium channel blockers nifedipine and verapamil. Pretreatment of the neurones with either dibutyryl cGMP or sodium nitroprusside (which elevates cGMP) inhibited bradykinin-induced formation of inositol phosphates. It is possible that cGMP could be involved in the regulation of polyphosphoinositide turnover in DRG neurones.
Burgess
G M
GM
Sandoz Institute for Medical Research, London, England.
Mullaney
I
I
McNeill
M
M
Coote
P R
PR
Minhas
A
A
Wood
J N
JN
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D002645:Chickens; D006152:Cyclic GMP / Q000502:physiology*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004987:Ethers / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000201:enzymology; D006162:Guanylate Cyclase / Q000378:metabolism*; D007295:Inositol Phosphates / Q000096:biosynthesis; D015759:Ionomycin; D007700:Kinetics; D009475:Neurons, Afferent / Q000187:drug effects / Q000201:enzymology*; D009599:Nitroprusside / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004987:Ethers; D007295:Inositol Phosphates; D011720:Pyrazoles; D009599:Nitroprusside; D003995:Dibutyryl Cyclic GMP; D015759:Ionomycin; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D002211:Capsaicin; D001920:Bradykinin; D002118:Calcium