Inhibition of a low K(m) GTPase activity in rat striatum by calmodulin

Glenn Jordan Treisman, N. Muirhead, L. Iwaniec, M. E. Gnegy

Research output: Contribution to journalArticle

Abstract

In rat striatum, the activation of adenylate cyclase by the endogenous Ca2+-binding protein, calmodulin, is additive with that of GTP but is not additive with that of the nonhydrolyzable GTP analog, guanosine-5'-(β, γ-imido)triphosphate (GppNHp). One possible mechanism for this difference could be an effect of calmodulin on GTPase activity which has been demonstrated to 'turn-off' adenylate cyclase activity. We examined the effects of Ca2+ and calmodulin on GTPase activity in EGTA-washed rat striatal particulate fractions depleted of Ca2+ and calmodulin. Calmodulin inhibited GTP hydrolysis at concentrations of 10-9-10-6 M but had no effect on the hydrolysis of 10-5 and 10-6 M GTP, suggesting that calmodulin inhibited a low K(m) GTPase activity. The inhibition of GTPase activity by calmodulin was Ca2+-dependent and was maximal at 0.12 μM free Ca2+. Maximal inhibition by calmodulin was 40% in the presence of 10-7 M GTP. The IC50 for calmodulin was 100 nM. In five tissues tested, calmodulin inhibited GTP hydrolysis only in those tissues where it could also activate adenylate cyclase. Calmodulin could affect the activation of adenylate cyclase by GTP in the presence of 3,4-dihydroxyphenylethylamine (DA, dopamine). Calmodulin decreased by nearly 10-fold the concentration of GTP required to provide maximal stimulation of adenylate cyclase activity by DA in the striatal membranes. The characteristics of the effect of calmodulin on GTPase activity with respect to Ca2+ and calmodulin dependence and tissue specificity parallel those of the activation of adenylate cyclase by calmodulin, suggesting that the two activities are closely related. Inhibition of a low K(m) GTPase activity by calmodulin could represent an action of calmodulin in increasing the association of a GTP-binding protein with the catalytic subunit activity resulting in a reduction of the 'turn-off' GTPase activity.

Original languageEnglish (US)
Pages (from-to)518-525
Number of pages8
JournalJournal of Neurochemistry
Volume44
Issue number2
StatePublished - 1985
Externally publishedYes

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GTP Phosphohydrolases
Calmodulin
Rats
Guanosine Triphosphate
Adenylyl Cyclases
Corpus Striatum
Hydrolysis
Chemical activation
Tissue
Dopamine
Calmodulin-Binding Proteins
Organ Specificity
Guanosine
Egtazic Acid
GTP-Binding Proteins
Inhibitory Concentration 50

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Inhibition of a low K(m) GTPase activity in rat striatum by calmodulin. / Treisman, Glenn Jordan; Muirhead, N.; Iwaniec, L.; Gnegy, M. E.

In: Journal of Neurochemistry, Vol. 44, No. 2, 1985, p. 518-525.

Research output: Contribution to journalArticle

Treisman, GJ, Muirhead, N, Iwaniec, L & Gnegy, ME 1985, 'Inhibition of a low K(m) GTPase activity in rat striatum by calmodulin', Journal of Neurochemistry, vol. 44, no. 2, pp. 518-525.
Treisman, Glenn Jordan ; Muirhead, N. ; Iwaniec, L. ; Gnegy, M. E. / Inhibition of a low K(m) GTPase activity in rat striatum by calmodulin. In: Journal of Neurochemistry. 1985 ; Vol. 44, No. 2. pp. 518-525.
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