Glial cells participate in histamine inactivation in vivo

Abstract

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 processes which determine the histamine concentration in the synaptic cleft. In vitro experiments showed that the glial metabolic toxin, fluoroacetate (20 and 40 mmol/l) depressed histamine uptake into cultured astroglial cells and dissociated hypothalamic cells of rats. For in vivo experiments, the push-pull superfusion technique was used. In anaesthetized rat, the anterior hypothalamic area was superfused through the push-pull cannula with artificial cerebrospinal fluid (aCSF) or with aCSF which contained fluoroacetate and the release of endogenous histamine was determined in the superfusate. Hypothalamic superfusion with fluoroacetate (20 mmol/l) led to a pronounced increase in extracellular histamine. The effect of fluoroacetate was inhibited by 5 micromol/l tetrodotoxin. Superfusion with Ca++-free, Mg++-rich (12 mmol/l) aCSF inhibited the basal release rate of histamine. Under these conditions, 20 mmol/l fluoroacetate did not modify the level of the amine in the superfusate. These data demonstrate that depression of glial function enhances the concentration of histamine in the extracellular space by slowing down the uptake of the amine into the glial cells. Thus, under in vivo conditions, glial cells are directly involved in the continuous removal of neuronal histamine from the synaptic cleft.

The human histaminergic system in neuropsychiatric disorders

“…Given that inhibition of astrocyte function may enhance the extracellular concentration of histamine, the astrocyte was proposed to be the main inactivation site of histamine [111,112]. However, in postmortem human PFC, despite the strong positive correlation between levels of HMT mRNA and mRNA levels of the astrocyte marker glial fibrillary acidic protein, both in controls and in patients with AD, HMT mRNA was localized only in neurons and not in astrocytes ( Figure I) [10].…”

Histamine (re)uptake by astrocytes: an experimental and computational study

“…Reports from Huszti´s laboratory described bidirectional [7][8][9] histamine uptake into cultured glial cells prepared from embryonic chicks [7] and neonatal rats [8][9][10] which was Na + -but not Cl --dependent [11]. Glial cells were also found to be involved in the continuous removal of neuronal histamine from the synaptic cleft in in vivo conditions [12]. In our previous work, we suggested that histamine is taken up into cultured neonatal rat astrocytes by at least two different transport systems [13].…”

Kinetic and pharmacological properties of [3H]-histamine transport into cultured type 1 astrocytes from neonatal rats

“…In order to demonstrate histamine uptake into cultured glial cells, astrocytes from neonatal (P0-P6) rats required maintenance in culture for at least 19 days [11,14]. Glial cells were also found to be involved in the continuous removal of neuronal histamine from the synaptic cleft in in vivo conditions [15].…”