Summary.
Inhibition of cAMP-dependent protein kinase (PKA) with N-[2-methylamino)ethyl]-5-isoquinolinesulfonamide (H-8) almost completely antagonized the increase in 5-HTP accumulation and 5-HIAA/5-HT ratio in hypothalamus induced by NAS-181, a 5-HT1B receptor antagonist, but had no effect when the mice were treated with NAS-181 together with WAY-100,635, a selective 5-HT1A receptor antagonist. Inhibition of Ca2+-calmodulin-dependent protein kinase (CaM kinase II) with the calmodulin antagonist N-(4-aminobutyl)-5-chloro-2-naphtalenesulfonamide (W-13) did not antagonise the effect of NAS-181 alone, but counteracted that evoked by the combined treatment with NAS-181 and WAY-100,635. The results indicate that activation of tryptophan hydroxylase by reducing the tone from terminal 5-HT1B receptors involves PKA whereas the depolarisation-induced activation of tryptophan hydroxylase involves CaM kinase II. The increase in the 5-HIAA/5-HT ratio may under the experimental conditions used suggest CaM kinase II-induced phosphorylation of synapsin I resulting in increased 5-HT release.
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Received November 26, 2001; accepted February 26, 2002 Published online June 28, 2002
Authors' address: Dr. C. Stenfors, AstraZeneca R&D Södertälje, S-151 85 Södertälje, Sweden, e-mail: carina.stenfors@astrazeneca.com
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Stenfors, C., Ross, S. Evidence for involvement of protein kinases in the regulation of serotonin synthesis and turnover in the mouse brain in vivo. J Neural Transm 109, 1353–1363 (2002). https://doi.org/10.1007/s00702-002-0732-5
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DOI: https://doi.org/10.1007/s00702-002-0732-5