Serotonin receptors on astrocytes in primary cultures: Effects of methysergide and fluoxetine

Abstract

A specific binding of serotonin (at least 50 fmol/mg protein) was demonstrated in mouse astrocytes in primary cultures. This binding was inhibited by methysergide and by fluoxetine.

Uptake and Binding of Serotonin by Primary Cultures of Mouse Astrocytes

“…This value is low, but it could be explained by the fact that the experiment was performed on intact cells forming a monolayer which ad hered to the plastic dish. The KD value of 6 [lM obtained by Scatchard analysis regarding partially purified membranes agrees with the evaluation (KD<30 \xM) of Hertz et al [11], This value, measured in the presence and ab sence of dBcAMP, showed that as in the case of uptake, cyclic nucleotides may act on bind ing processes so as to increase the affinity of astrocytes for 5-HT. In other words, binding was inhibited by methysergide, an observa tion agreeing with Hertz et al [11], That sub stance was less active, however, since we found an IC50 of 10-5 M (compared to total neuronal inhibition at 5 /zM).…”

“…Methysergide was reported to inhibit neuronal 5-HT binding [11]. However, in this study, methysergide inhibited glial 5-HT transport in a competi tive manner, since high 5-HT concentrations led to a value equivalent to the control (table II).…”

“…In addition to the 5-HT transport process, astrocytes are able to bind 3H-5-HT to their membranes. Hertz et al [11] reported such binding on intact astrocytes, but could not find more than 30% specific binding in the presence of 50 ¡jlM nonradioactive 5-HT. This value is low, but it could be explained by the fact that the experiment was performed on intact cells forming a monolayer which ad hered to the plastic dish.…”

“…These results were confirmed by Fillion et al [8], who proposed possible partici pation of glia corresponding to one of these binding sites. Hertz et al [11] reported sim ilar binding on glial cells obtained in primary cultures, but they worked directly with a monolayer adhering to the plastic dish and binding represented only 30% of the total. The existence of a glial receptor is not an ac cepted concept and must be confirmed.…”

Neurons from substantia nigra increase the efficacy and potency of second messenger arising from striatal astroglia dopamine receptor

“…Identification of receptors for neurotransmitters and neuromodulators on astroglial cells (Hansson et al, 1987;Henn et al, 1977;Hertz et al, 1979;Murphy and Pearce, 1987;Trimmer et al, 1984;Van Calker and Hamprecht, 1980) and identification of their second messenger systems may open new possibilities for determining and, thereafter, regulating specific metabolic pathways. It would provide a much clearer understanding of the functions of astroglia and their intercellular connections in the nervous system.…”