beta-Agkistrodotoxin inhibition of Ca2+-dependent release of glutamate, aspartate, glycine and gamma-aminobutyric acid from cerebrocortical synaptosomes following its binding to synaptic membrane.
The binding properties of beta-AgTX, a snake pre-synaptic toxin, membranes and its effect on transmitter release from cerebrocortical synaptosomes were investigated. Assay of [125I]-beta-AgTX binding to rat synaptic membrane revealed a high affinity binding site for the toxin within the synaptic membrane. Preincubation with beta-AgTX inhibited K+-evoked Ca2+-dependent glutamate release from synaptosomes in a concentration-dependent manner, as determined by an on-line enzyme-linked fluorometric assay. The toxin also blocked the Ca2+-dependent release of other transmitters, aspartate, glycine, and GABA induced by K+-depolarization. However, Ca2+-ionophore, ionomycin-stimulated Ca2+-dependent transmitter release was not significantly affected by beta-AgTX, indicating that the toxin inhibits transmitter release by reducing the entry of Ca2+ into cytoplasm. It is suggested that beta-AgTX-binding site in synaptic membrane is related to the release of a variety of transmitters.
Zhang
Yong-Quan
YQ
Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, 200031, Shanghai, P. R. China.
Zhou
Yuan-Cong
YC
Shen
Guo-Guang
GG
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001665:Binding Sites / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003435:Crotalid Venoms / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D007457:Iodine Radioisotopes; D008297:Male; D008954:Models, Biological; D009498:Neurotoxins / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013574:Synaptosomes; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D003435:Crotalid Venoms; D007457:Iodine Radioisotopes; D009498:Neurotoxins; D018377:Neurotransmitter Agents; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C070121:beta-agkistrodotoxin; D002118:Calcium; D005998:Glycine