Effects of staurosporine on Ca2+-dependent and Ca2+-independent [14C]GABA release from rat brain synaptosomes |
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Authors: | L G Storchak N G Pozdnyakova N H Himmelreich |
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Institution: | (1) Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine |
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Abstract: | The effect of a protein kinase inhibitor, staurosporine, on Ca2+-dependent and Ca2+-independent release of 14C]GABA in isolated rat brain synaptosomes was studied. Calcium-dependent 14C]GABA release was stimulated by depolarization with a K+ channel blocker, 4-aminopyridine (4-AP), or high K+ concentration. It has been shown that the effect of 4-AP is Ca2+-dependent, while high K+ is able to evoke 14C]GABA release in both Ca2+-dependent and Ca2+-independent manners. In addition, Ca2+-independent 14C]GABA release was studied using α-latrotoxin (LTX) as a tool. Pretreatment of synaptosomes with staurosporine resulted in
pronounced inhibition of 4-AP-stimulated Ca2+-dependent 14C]GABA release. The inhibitory effect of staurosporine on 14C]GABA release was not due to modulation of 4-AP-promoted45Ca2+ influx into synaptosomes. If the process of 14C]GABA release occurred in the Ca2+-independent manner irrespectively of what, LTX or high K+, stimulated this process, it was not inhibited by staurosporine. Considering the above findings, it is reasonable to assume
that the absence of Ca2+ in the extracellular medium created conditions for activation of the process of neurotransmitter release without Ca2+-dependent dephosphorylation of neuronal phosphoproteins; as a consequence, regulation of exocytotic process was modulated
in such a manner that inhibition of protein kinases did not disturb exocytosis. |
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