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Kuhn DM, O'Callaghan JP, Juskevich J, Lovenberg W.
“Activation of Brain Tryptophan Hydroxylase by ATP-Mg2+: Dependence on Calmodulin”.
Proc.Natl Acad. Sci.. 1980;77(8):4688-91.
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Abstract
The dependence on calmodulin of tryptophan hydroxylase (EC 1.14.16. 4) activation by ATP-Mg2+ in brain was studied. Methods Tryptophan hydroxylase was assayed in male rat (150-200 g) mesencephalic tegmentum tissue by a modified Friedman procedure. The enzyme is activated by ATP-Mg2+ in a manner which depends on Ca but not on cAMP. Brain calmodulin was purified by affinity chromatography on fluphenazine-Sepharose. Proteins were separated by electrophoresis in NaDodSO4/ polyacrylamide gel slabs. Results All the drugs tested (10-100 mcM) exerted some degree of inhibition on tryptophan hydroxylase activation by ATP-Mg2+. The inhibitory potency was in the order: pimozide (McNeil) > fluphenazine (Squibb) > trifluoperazine (SK+F) > cis flupenthixol (Lundbeck) > haloperidol > penfluridol (both McNeil) > chlorpromazine (SK+F). Drugs which had no effect on the enzyme activation included theophylline, morphine, naloxone, LSD, desmethylimipramine and propranolol. The addition of external purified calmodulin protected the enzyme from effects due to the drugs. Tryptophan hydroxylase prepared by affinity chromatography and free of calmodulin was not activated by ATP-Mg2+ but if calmodulin was then added to the enzyme, the latter was reactivated byATP-Mg2+ providing Ca2+ was present. Conclusion Tryptophan hydroxylase activation under phosphorylating conditions depends on both calmodulin and Ca2+.
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