Nitric Oxide Regulates Cyclic GMP‐Dependent Protein Kinase Phosphorylation in Rat Brain

• Published in: Journal of neurochemistry Vol. 71; no. 2; pp. 676 - 683
• Main Authors: El‐Husseini, Alaa El‐Din, Bladen, Christopher, Williams, Julie A., Reiner, Peter B., Vincent, Steven R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.08.1998; Blackwell
• Subjects: Animals; Arousal; Arousal - physiology; Biochemistry and metabolism; Biological and medical sciences; Central nervous system; Cyclic GMP; Cyclic GMP - analogs & derivatives; Cyclic GMP - metabolism; Cyclic GMP - pharmacology; Cyclic GMP-Dependent Protein Kinases - analysis; Cyclic GMP-Dependent Protein Kinases - antagonists & inhibitors; Cyclic GMP-Dependent Protein Kinases - metabolism; Cyclic GMP‐dependent protein kinase; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; GABA Modulators - pharmacology; Indazoles - pharmacology; Male; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase - antagonists & inhibitors; Pentobarbital - pharmacology; Phosphorylation; Rats; Rats, Wistar; Thalamus; Thalamus - enzymology; Vertebrates: nervous system and sense organs; Phosphorylation; Rat; Enzyme; Transferases; Rodentia; Central nervous system; 3',5'-GMP; Vertebrata; Mammalia; Protein kinase; Nitric oxide; Arousal; Thalamus; Brain (vertebrata)
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1998.71020676.x

: 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.