Uptake and Binding of Serotonin by Primary Cultures of Mouse Astrocytes

Abstract

Primary cultures of glia contain a high glial fibrillary acidic protein level and exhbit important glutamine synthetase activity. They take up serotonin via a high affinity carrirer-mediated system with a K_m of micromolar range. The K_m of this transport process does not vary during cell growth or maturation; however, during the last period of morphological change induced by dibutyryl cyclic AMP, an increase in V_max is observed. Chlorimipramine, fluoxetine and fenfluramine at 10^-4M inhibit this uptake. ³H-5-HT still binds to partially purified astrocytic membranes on a single type of site. During growth, neither K_D nor B_max were modified. During the maturation period, K_D decreased to about 50% of its control level. Methysergide inhibits that binding.

Expression of preproenkephalin mRNA by cultured astrocytes and neurons.

“…Although astrocytes express receptors for neurotransmitters (6,(15)(16)(17)(18)(19) and contain systems for neurotransmitter uptake (3-7), they do not appear to synthesize neurotransmitters themselves. With the exception of the amino acid transmitters, it is generally accepted that neurotransmitters in brain are localized within neurons.…”

“…Proliferation of astrocytes plays an integral part in the healing of brain injury, and interactions between neurons and astrocytes regulate neuronal differentiation and process elongation (9-13). Studies of cell surface molecules expressed by astrocytes have shown at least two identifiable subtypes (14), and there is some evidence that there are differences among astrocytes from different regions of the brain (10).Although astrocytes express receptors for neurotransmitters (6,(15)(16)(17)(18)(19) and contain systems for neurotransmitter uptake (3-7), they do not appear to synthesize neurotransmitters themselves. With the exception of the amino acid transmitters, it is generally accepted that neurotransmitters in brain are localized within neurons.…”

“…Astrocytes may help to regulate the ionic environment of the extracellular space (1)(2)(3), to inactivate neurotransmitters by accumulating them (3)(4)(5)(6)(7), and to transfer nutrients and neurotransmitter precursors to neurons (8,9). Proliferation of astrocytes plays an integral part in the healing of brain injury, and interactions between neurons and astrocytes regulate neuronal differentiation and process elongation (9)(10)(11)(12)(13).…”

Serotoninergic control of the activity and expression of glial GABA transporters in the rat cerebellum

“…Serotonin may regulate the mRNA expression of different GATs by a common intracellular pathway since the percentage of mRNA increase was similar for each transporter. Two main pathways may be involved, either a direct intracellular action of 5-HT via astrocytic 5-HT uptake (Anderson et al, 1992;Kimelberg and Katz, 1985;Tardy et al, 1982) or an effect via 5-HT receptors and second messenger pathways. There is growing evidence that intracellular second messenger pathways can modulate GABA transport, as shown in glial cell cultures (Clark and Amara, 1993;Gomeza et al, 1991).…”

Developing rat cerebellum: Glutamine and glutamate influx correlated to the cellular distribution of glutamine synthetase

“…This hypothesis is also supported by the low levels of Gls activity found by Patel et al 18 in rat cerebellum during the first week of postnatal life when a large proportion of neuroblasts are replicating and by the data of other authors in cultured astrocytes cells. 14,19 The rapid increase, on a per cerebellum basis, of the capacity to take up Gin during the first postnatal week, when cell division occurs at a moderate rate, might correspond to the necessity to accumulate nucleic acid precursors before the burst of multiplication of EGL cells during the second postnatal week.…”