Thymopentin antagonizes stress-induced changes of GABA/benzodiazepine receptor complex.

Intraperitoneal administration of thymopentin, a thymopentin II-derived pentapeptide, had no stable and evident effect in the two anxiety models (elevated plus-maze and licking-conflict test) studied. However, in the elevated plus-maze test thymopentin antagonized the behavioral effects of DMCM, a beta-carboline derivative with anxiogenic properties. Further, it was demonstrated that the licking-conflict test procedure itself produced a significant elevation of plasma corticosterone levels, increased the number of [3H]flunitrazepam and decreased the number of [3H]muscimol binding sites in rat hippocampus. The forced-swimming stress similarly to the licking-conflict test also caused an increase in hippocampal [3H]flunitrazepam binding sites. Although ineffective behaviorally in the tests for anxiety, thymopentin pretreatment effectively reversed the changes in corticosterone levels caused by the licking-conflict test. Moreover, it normalized the changed number of benzodiazepine and GABA receptors after stressful stimuli. It is well known that not all anxiolytic drugs (i.e. buspirone) are equally active in behavioral tests for anxiety. According to our data we propose that thymopentin has stress-protective activity. As in vivo and in vitro thymopentin did not change [3H]-flunitrazepam and [3H]muscimol binding, the direct effect of this peptide on the GABA-benzodiazepine-Cl- ionophore receptor complex is unlikely. The action of this peptide on GABA release and/or metabolism can be suggested.

[Thymus hormones--precursors of new psychoneuromodulatory peptides]. / Timusnye gormony--predshestvenniki novykh psikhoneiromoduliruiushchikh peptidov.

The influence of thymic hormone's short fragments: thymopentin or T-5 (RKDVY), RKD and SKD, on behaviour and neurochemical processes (contents of GABA and monoamines in the brain and adrenals, plasma corticosterone), was investigated. The 100 and 500 micrograms/kg doses i.p. prevented alterations in rat's brain GABA content and plasma corticosterone level, as well as elicited anxiolytic activity in a conflict test. T-5 exerted antidepressant activity, too. SKD potentiated the haloperidol-induced catalepsy. The data obtained suggest a multicomponent (CNS-activating and inhibiting) mechanism of action of the thymic hormone fragments. These fragments seem to be formed endogenously during thymic hormone bioprocessing and may act as regulatory neuropeptides.

[Neuroimmunoregulatory properties of short protein fragments in rats exposed to immobilization stress]. / Neiroimmunoreguliruiushchie svoistva korotkikh fragmentov belkov v usloviiakh immobilizatsionnogo stressa u krys.

The influence of short protein fragments on immobilization stress-induced alterations in neuroendocrine and immune systems (catecholamine content in the striatum, hypothalamus and adrenals, serum corticosterone concentration, specific antibody producing activity) was investigated. Immunoglobulin G fragments--tuftsin, rigin, polar amino acid set--polarin and thymus hormone fragment--thymopoetin, as well as substance P (as reference drug) were administered intraperitoneally at doses of 100 and 500 micrograms/kg 30 min before exposure to stress. Rigin and thymopentin showed high stress-protective activity. It is suggested that similar protein fragments, being endogenously formed, may play a regulating role in neuroimmunological homeostasis during exposure to stress.