Regulation of the Serotonergic System by Kainate in the Avian Retina

Serotonin (5-HT) has been recognized as a neurotransmitter in the vertebrate retina, restricted mainly to amacrine and bipolar cells. It is involved with synaptic processing and possibly as a mitogenic factor. We confirm that chick retina amacrine and bipolar cells are, respectively, heavily and faintly immunolabeled for 5-HT. Amacrine serotonergic cells also co-express tyrosine hydroxylase (TH), a marker of dopaminergic cells in the retina. Previous reports demonstrated that serotonin transport can be modulated by neurotransmitter receptor activation. As 5-HT is diffusely released as a neuromodulator and co-localized with other transmitters, we evaluated if 5-HT uptake or release is modulated by several mediators in the avian retina. The role of different glutamate receptors on serotonin transport and release in vitro and in vivo was also studied. We show that L-glutamate induces an inhibitory effect on [³H]5-HT uptake and this effect was specific to kainate receptor activation. Kainate-induced decrease in [³H]5-HT uptake was blocked by CNQX, an AMPA/kainate receptor antagonist, but not by MK-801, a NMDA receptor antagonist. [³H]5-HT uptake was not observed in the presence of AMPA, thus suggesting that the decrease in serotonin uptake is mediated by kainate. 5-HT (10-50 μM) had no intrinsic activity in raising intracellular Ca²⁺, but addition of 10 μM 5-HT decreased Ca²⁺ shifts induced by KCl in retinal neurons. Moreover, kainate decreased the number of bipolar and amacrine cells labeled to serotonin in chick retina. In conclusion, our data suggest a highly selective effect of kainate receptors in the regulation of serotonin functions in the retinal cells.