Tetanus toxin-induced protein kinase C activation and elevated serotonin levels in the perinatal rat brain.
A single intracerebral injection of tetanus toxin (TeTox) is able to produce a time-dependent translocation of Ca2(+)-phosphatidylserine-dependent protein kinase C (PKC) in close-to-term rat brain. TeTox-triggered translocation of PKC is dose- and time-dependent, can be prevented by tetanus antitoxin, and does not occur upon administration of toxin fragments B and C. TeTox-triggered PKC translocation is accompanied by a time-dependent increase in brain serotonin (5-HT). Increase of brain 5-HT is independent of monoamine oxidase inhibition by pargyline. Phorbol ester and TeTox cause a significant increase in serotonin while H-7, a kinase inhibitor, does not affect serotonin levels but abolishes the effect of TeTox. Gangliosides prevent TeTox-triggered 5-HT increase. The data are consistent with the possibility that TeTox acts effectively on the serotonergic innervation, presumably in conjunction with PKC to cause accumulation of serotonin.
Aguilera
J
J
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Lopez
L A
LA
Yavin
E
E
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D007700:Kinetics; D011247:Pregnancy; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012701:Serotonin / Q000378:metabolism*; D013743:Tetanus Antitoxin / Q000494:pharmacology; D013744:Tetanus Toxin / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D013743:Tetanus Antitoxin; D013744:Tetanus Toxin; D012701:Serotonin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate