Document Detail

The interaction of tetanus toxin with intact bovine adrenal chromaffin cells: binding of toxin and subsequent inhibition of catecholamine release.
MedLine Citation:
PMID:  1445928     Owner:  NLM     Status:  MEDLINE    
Tetanus toxin (about 1 nM) inhibits 70% of the nicotine-evoked release of catecholamines from intact adrenal medullary chromaffin cells after 20 h of incubation and 30% of the K(+)-evoked release. Inhibition of Ca(2+)-evoked release from detergent-permeabilized cells requires higher concentrations of toxin (about 1 microM) toxin, but is maximal after 12 min. Preincubation of the intact cells with ganglioside GT1 in the absence of toxin also inhibits evoked secretion. 125I-labelled toxin bound specifically to these cells; the binding capacity was greater at pH 6 (about 1 pmol toxin/mg cell protein) than at pH 7.4 (about 0.25 pmol). In both cases there were at least two binding components: one of high affinity (Kd about 1 nM) accounting for about 20% of total binding and one of lower affinity (Kd 10-20 nM). Preincubation of the cells with ganglioside increased the binding capacity, but did not affect the Kd of the lower affinity component. Similar observations could be made when binding was measured immunocytochemically. Extraction of gangliosides from chromaffin cells and overlay experiments with radiolabelled toxin showed that, as well as GM3, the major ganglioside component of chromaffin cell membranes, a ganglioside having the chromatographic mobility of GT1 was a major ligand for toxin.
C A Colville; M K Bansal; J H Phillips; S van Heyningen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1137     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  1992 Nov 
Date Detail:
Created Date:  1992-12-30     Completed Date:  1992-12-30     Revised Date:  2009-09-29    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  264-73     Citation Subset:  IM    
Department of Biochemistry, University of Edinburgh, George Square, UK.
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MeSH Terms
Adrenal Medulla / cytology,  drug effects,  metabolism*
Catecholamines / metabolism*
Cells, Cultured
Chromaffin Granules / drug effects,  metabolism*
Chromatography, Thin Layer
G(M3) Ganglioside / metabolism
Gangliosides / pharmacology
Tetanus Toxin / metabolism*,  pharmacology
Grant Support
//Wellcome Trust
Reg. No./Substance:
0/Catecholamines; 0/G(M3) Ganglioside; 0/Gangliosides; 0/Tetanus Toxin; 59247-13-1/trisialoganglioside GT1

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