Nitric oxide regulates cyclic GMP-dependent protein kinase phosphorylation in rat brain.
Nitric oxide (NO) acts via soluble guanylyl cyclase to increase cyclic GMP (cGMP), which can regulate various targets including protein kinases. Western blotting showed that type II cGMP-dependent protein kinase (cGK II) is widely expressed in various brain regions, especially in the thalamus. In thalamic extracts, the phosphorylation of several proteins, including cGK II, was increased by exogenous NO or cGMP. In vivo pretreatment with a NO synthase inhibitor reduced the phosphorylation of cGK II, and this could be reversed by exogenous NO or cGMP. Conversely, brainstem electrical stimulation, which enhances thalamic NO release, caused a NO synthase-dependent increase in the phosphorylation of thalamic cGK II. These results indicate that endogenous NO regulates cGMP-dependent protein phosphorylation in the thalamus. The activation of cGKII by NO may play a role in thalamic mechanisms underlying arousal.
Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, Canada.
A E
AE
El-Husseini
C
C
Bladen
J A
JA
Williams
P B
PB
Reiner
S R
SR
Vincent
D000818:Animals; D001143:Arousal / Q000502:physiology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010424:Pentobarbital / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013788:Thalamus / Q000201:enzymology*
D004791:Enzyme Inhibitors; D018757:GABA Modulators; D007191:Indazoles; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D010424:Pentobarbital; C080122:7-nitroindazole