Tetanus toxin‐induced protein kinase C activation and elevated serotonin levels in the perinatal rat brain

[摘要]

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-tenn 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 timedependent 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.

[学科分类] 生物化学/生物物理

[关键词] Tetanus toxin;Serotonin;Protein kinase C;Ganglioside;Brain development;H-7;1-(5-isoquinolinylsulfonyl)-2-methylpiperazine;GM 1 galactosyl-N-acetylgalactosaminyl-(N acetylneuraminyl)-galactosylglucosylceramide;GDlb galactosyl-Macetylgalactosaminyl-(N-acetylneuraminyl-N-acetymeuraminyl)galactosylglucosylceramide;BBG;bovine brain ganglioside mixture;TPA;12-O-tetra-decanoyl-phorbol-13-acetate;PKC Ca2+-phosphatidylserinedependent protein kinase C;TeTox;tetanus toxin