General Paper
Serotonin-induced decrease in brain ATP, stimulation of brain anaerobic glycolysis and elevation of plasma hemoglobin; the protective action of calmodulin antagonists

https://doi.org/10.1016/0306-3623(94)90147-3Get rights and content

Abstract

1. Injection of serotonin (5-hydroxytryptamine) to rats, induced a dramatic fall in brain ATP level, accompanied by an increase in Pi. Concomitant to these changes, the activity of cytosolic phosphofructokinase, the rate-limiting enzyme of glycolysis, was significantly enhanced. Stimulation of anaerobic glycolysis was also reflected by a marked increase in lactate content in brain.

2. Brain glucose 1,6-bisphosphate level was decreased, whereas fructose 2,6-bisphosphate was unaffected by serotonin.

3. All these serotonin-induced changes in brain, which are characteristic for cerebral ischemia, were prevented by treatment with the calmodulin (CaM) antagonists, trifluoperazine or thioridazine.

4. Injection of serotonin also induced a marked elevation of plasma hemoglobin, reflecting lysed erythrocytes, which was also prevented by treatment with the CaM antagonists.

5. The present results suggest that CaM antagonists may be effective drugs in treatment of many pathological conditions and diseases in which plasma serotonin levels are known to increase.

References (34)

Cited by (12)

  • Monoamine involvement in the antidepressant-like effect induced by P2 blockade

    2017, Brain Research
    Citation Excerpt :

    Evidences indicate that ATP itself is also able to attenuate serotonin release in rat brain cortex via P2R activation (Von Kügelgen et al., 1997). Conversely, serotonin is also able to modulate ATP levels in the brain (Koren-Schwartzer et al., 1994). In this context, the add-on effect observed with concomitant PPADS and FLX administration could derive from P2R blockade favoring serotonergic availability.

View all citing articles on Scopus
View full text