Yx. Tao et Ra. Johns, Activation of cGMP-dependent protein kinase I alpha is required for N-methyl-D-aspartate- or nitric oxide-produced spinal thermal hyperalgesia, EUR J PHARM, 392(3), 2000, pp. 141-145
The effect of a selective cyclic guanocine 3',5'-monophosphate (cGMP)-depen
dent protein kinase I alpha inhibitor, Rp-8-[(4-chlorophenyl)thio]-cGMPS tr
iethylamine (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. I
ntrathecal administration of NMDA (15 pg/10 mu l) or NOC-12 (10, 20 and 30
mu g/10 yl) produced a marked curtailment of the tail-flick latency. Maxima
l NMDA- or NOC-12-produced facilitation of the tail-flick reflex was signif
icantly and dose-dependently blocked by intrathecal pretreatment with Rp-8-
p-CPT-CGMPS (7.5, 15 and 30 mu g/10 mu l). 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 lot is required for NMDA-
or NO-produced facilitation of thermal hyperalgesia at the spinal cord leve
l. (C) 2000 Elsevier Science B.V. All rights reserved.