GLIAL-CELLS PARTICIPATE IN HISTAMINE INACTIVATION IN-VIVO

The ability of glial cells to take up histamine in vitro suggests that these cells may be involved in histamine inactivation. This prompted us to study the possible interactions between neuronal and glial proce sses which determine the histamine concentration in the synaptic cleft . In vitro experiments showed that the glial metabolic toxin, fluoroac etate (20 and 40 mmol/l) depressed histamine uptake into cultured astr oglial cells and dissociated hypothalamic cells of rats. For in vivo e xperiments, the push-pull superfusion technique was used. In anaesthet ized rat, the anterior hypothalamic area was superfused through the pu sh-pull cannula with artificial cerebrospinal fluid (aCSF) or with aCS F which contained fluoroacetate and the release of endogenous histamin e was determined in the superfusate. Hypothalamic superfusion with flu oroacetate (20 mmol/l) led to a pronounced increase in extracellular h istamine. The effect of fluoroacetate was inhibited by 5 mu mol/l tetr odotoxin. Superfusion with Ca++-free, Mg++-rich (12 mmol/l) aCSF inhib ited the basal release rate of histamine. Under these conditions, 20 m mol/l fluoroacetate did not modify the level of the amine in the super fusate. These data demonstrate that depression of glial function enhan ces the concentration of histamine in the extracellular space by slowi ng down the uptake of the amine into the glial cells. Thus, under in v ivo conditions, glial cells are directly involved in the continuous re moval of neuronal histamine from the synaptic cleft.