Activation of cGMP-dependent protein kinase Ialpha is required for N-methyl-D-aspartate- or nitric oxide-produced spinal thermal hyperalgesia.

Abstract

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.

• Authors: Y X Tao, R A Johns
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 392 Issue 3 Pg. 141-5 (Mar 31 2000) ISSN: 0014-2999 [Print] Netherlands
• PMID: 10762667 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphorothioate
• Enzyme Inhibitors
• NOC 12
• Nitric Oxide Donors
• Nitroso Compounds
• Thionucleotides
• Nitric Oxide
• N-Methylaspartate
• Cyclic GMP-Dependent Protein Kinase Type I
• Cyclic GMP-Dependent Protein Kinases
• Cyclic GMP

Topics

• Animals
• Cyclic GMP (analogs & derivatives, pharmacology)
• Cyclic GMP-Dependent Protein Kinase Type I
• Cyclic GMP-Dependent Protein Kinases (antagonists & inhibitors, metabolism)
• Dose-Response Relationship, Drug
• Enzyme Activation
• Enzyme Inhibitors (pharmacology)
• Hyperalgesia (chemically induced, physiopathology)
• Injections, Spinal
• Male
• N-Methylaspartate (pharmacology)
• Nitric Oxide (physiology)
• Nitric Oxide Donors (pharmacology)
• Nitroso Compounds (pharmacology)
• Pain (chemically induced, physiopathology)
• Pain Measurement
• Rats
• Rats, Sprague-Dawley
• Thionucleotides (pharmacology)