Activation of cGMP-dependent protein kinase Ialpha is required for N-methyl-D-aspartate- or nitric oxide-produced spinal thermal hyperalgesia.
The effect of a selective cyclic guanocine 3',5'-monophosphate (cGMP)-dependent protein kinase Ialpha inhibitor, Rp-8-[(4-chlorophenyl)thio]-cGMPS triethylamine (Rp-8-p-CPT-CGMPS), on either N-methyl-D-aspartate (NMDA)- or N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino)ethanamine (NOC-12, a nitric oxide (NO) donor)-produced thermal hyperalgesia was examined in the rat. Intrathecal administration of NMDA (15 pg/10 microl) or NOC-12 (10, 20 and 30 microg/10 microl) produced a marked curtailment of the tail-flick latency. Maximal NMDA- or NOC-12-produced facilitation of the tail-flick reflex was significantly and dose-dependently blocked by intrathecal pretreatment with Rp-8-p-CPT-CGMPS (7.5, 15 and 30 microg/10 microl). Rp-8-p-CPT-CGMPS given alone did not markedly alter baseline tail-flick latency. These results suggest that the activation of cGMP-dependent protein kinase Ialpha is required for NMDA- or NO-produced facilitation of thermal hyperalgesia at the spinal cord level.
Tao
Y X
YX
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287-4965, USA.
Johns
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RA
D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D007278:Injections, Spinal; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D013873:Thionucleotides / Q000494:pharmacology
C090860:8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphorothioate; D004791:Enzyme Inhibitors; C118603:NOC 12; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D013873:Thionucleotides; D009569:Nitric Oxide; D016202:N-Methylaspartate; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP