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Protein Phosphorylation and Calcium Uptake into Rat Forebrain Synaptosomes: Modulation by the σ Ligand, 1,3‐Ditolylguanidine
Author(s) -
Brent Paul J.,
Herd Lynn,
Saunders Heather,
Sim Alistair T. R.,
Dunkley Peter R.
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.68052201.x
Subject(s) - chemistry , depolarization , sodium nitroprusside , calcium , protein kinase c , phosphorylation , protein kinase a , synaptosome , biophysics , calcium channel , biochemistry , nitric oxide , medicine , endocrinology , biology , organic chemistry
Abstract: The σ ligand 1,3‐di‐ O ‐tolylguanidine (DTG) increased basal dynamin and decreased depolarization‐stimulated phosphorylation of the synaptosomal protein synapsin Ib without having direct effects on protein kinases or protein phosphatases. DTG dose‐dependently decreased the basal cytosolic free Ca 2+ concentration ([Ca 2+ ] i ) and blocked the depolarization‐dependent increases in [Ca 2+ ] i . These effects were inhibited by the σ antagonists rimcazole and BMY14802. The nitric oxide donors sodium nitroprusside (SNP) and 8‐( p ‐chlorophenylthio)guanosine‐3′,5′‐cyclic monophosphorothioate decreased basal [Ca 2+ ] i and the KCl‐evoked rise in [Ca 2+ ] i to an extent similar to DTG. SNP, but not DTG, produced a rise in cyclic GMP levels, suggesting that the effect of DTG on [Ca 2+ ] i was not mediated via downstream regulation of cyclic GMP levels. DTG increased 45 Ca 2+ uptake and efflux under basal conditions and inhibited the 45 Ca 2+ uptake induced by depolarization with KCl. The KCl‐evoked rise in [Ca 2+ ] i was inhibited by ω‐conotoxin (ω‐CgTx)‐GVIA and ‐MVIIC but not nifedipine and ω‐agatoxin‐IVA. The effect of DTG on decreasing the KCl‐evoked rise in [Ca 2+ ] i was additive with ω‐CgTx‐MVIIC but not with ω‐CgTx‐GVIA. These data suggest that DTG was producing some of its effects on synapsin I and dynamin phosphorylation and intrasynaptosomal Ca 2+ levels via inhibition of N‐type Ca 2+ channels.