Mechanism of Action of the Presynaptic Neurotoxin, Tetanus Toxin

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Abstract:

During the early phase of this project we were successful in establishing a cultured cell model system, the PC12 pheochromocytoma cell line, to study the mechanism of action of tetanus toxin. Further we have studied the characteristics of the intoxication pathway Sandberg et al. 1989 and have found that it is analogous to that which has been characterized, to some extent, in vivo Simpson, 1986 Habermann and Dreyer, 1986. The major thrust during the past year was to exploit this well characterized model system to gain insight into the molecular mechanism of action of tetanus toxin. In the present study, we have utilized a preparation of permeabilized, NGF-differentiated, PC12 cells to examine the role of cGMP in neurotransmitter release. An important finding is that cGMP can stimulate neurotransmitter release from such cells in a Ca2- independent manner. Further, NGF-differentiated PC12 cells show two phases of vesicular neurotransmitter release that can be distinguished not only by their differential sensitivity to Ca2, but also in their sensitivity to cGMP.

Author(s):
Rogers, Terry B.
Author Organization(s):
MARYLAND UNIV BALTIMORE SCHOOL OF MEDICINE
Descriptive Note:
Annual rept. 1 Apr 1989-30 Jun 1990
Pagination:
0022

Security Markings

DOCUMENT & CONTEXTUAL SUMMARY

Distribution:
Approved For Public Release

RECORD

Collection: TR
Identifying Numbers
Contract/Grant Number(s):
DAMD17-86-C-6160
Task Number(s):
AA
Project Number(s):
3M162787A871
Monitor Series:
USAMRDC
 Subject Terms
Joint Capability Areas:
JCA_1_Force Support; JCA_1.3_Human Capital Management; JCA_1.2.7_Experimentation; JCA_1.3.2_Personnel Management; JCA_1.2.5_Lessons Learned; JCA_3_Force Application; JCA_3.2_Engagement
Communities of Interest:
No COI(s) Identified
Descriptor(s):
*MODELS, MOLECULES, CELLS, GAIN, RELEASE, IN VIVO ANALYSIS, NEUROTRANSMITTERS, TOXINS AND ANTITOXINS, TETANUS, INTOXICATION
Field(s)/Group(s):
Medicine and Medical Research, Toxicology, Pharmacology, Biomedical Instrumentation and Bioengineering
Keyword(s):
*TETANUS, *TOXINS AND ANTITOXINS, BIOTECHNOLOGY, NEUROTOXINS, PRESYNAPTIC TOXIN, LAB ANIMALS, MICE, RA I, MEMBRANE MODELS, TOXICOLOGY, PE62787A, WUDA309811, WU382, AS871
Report Date:
1990 Apr 30