Histamine is classified as a biogenic amine and is found in many tissues in the body. In the central nervous system, it plays the role of a nerve transporter. All neurotransmitters are thought to be neurotoxic at excess concentrations. So after release into synaptic cleft and interaction with receptor they should be removed from synapses by release into extracellular fluid, re-uptake into cells from which they have been released or uptake, into the glia cells surrounding the synapse. Astrocytes, which together with the presynaptic and postsynaptic nerve cells, form a three-part synapse, thus play an important role in the inactivation and removal of histamine from the synaptic cleft.
Since the histamine molecule is positively charged under physiological conditions (pH 7.4), it needs to be transported by transporter through membrane. Although there is already a lot known about histamine uptake, the specific transporter remains unknown. Therefore, we decided to investigate histamine uptake in astrocytes isolated from the cerebral cortex of a newborn rat.
We first came to the conclusion that the uptake of histamine into neonatal rat astrocytes is a concentration-dependent and ph-dependent process. At more acidic pH, both affinity and capacity for histamine uptake into astrocytes decreased, and uptake was still greater in the range of higher concentrations of 3H-histamine added.
We came to a conclusion that histamine is transported in astrocytes from cerebral cortex of neonatal rat by low-affinity and high-capacity transporter system. The results of inhibition of histamine uptake into astrocytes by decinium 22, which is an inhibitor of the organic cation transporter, have shown that histamine is very likely to be transmitted via the organic cation transporter. Decinium 22 in concentration of 100 mM almost completely inhibited histamine uptake into astrocytes.
We also examined the effect of other monoamines on histamine uptake into neonatal rat astrocytes and found that dopamine had the greatest influence. Therefore, we were also interested in the influence of dopamine precursors and dopamine-like substances. Substances entering dopaminergic neurons – tyrosine, 6-hydroxydopamine and selegiline – have been shown to reduce the uptake of histamine into neonatal rat astrocytes more than membrane-acting agents – apomorphine and L-DOPA – which had little effect on uptake.