Serotonin (5-Hydroxytryptamine, 5-HT) can , in many ways, be considered one of the most pervasive and potent regulatory neurotransmitter systems in the mammalian brain. The diversity and selectivity of the receptors which respond to serotonin are evidence of the fine controlling role which this neurotransmitter plays in normal brain function. In our work, we have localized a high affinity serotonin receptor (5-HT1) to astroglial cells. These cells surround neurons and play a vital role in their maintenance as well as in modulating their transmitting activity. We now wish to extend our original studies into several important new areas, including: 1) identification of the receptor subtype, i.e., 5-HT1A, 5-HT1B or 5-HT1C receptor 2) identification of the second messenger linkage, and 3) role of these receptors in development of serotonergic neurons. As a source of astroglial cells, we use primary cultures derived from newborn rat brain. Astrocytes derived from brainstem and cortex will be examined. First, we will establish the sub-type of serotonin receptor localized to astrocytes by using the specific receptor ligands 3H-PAT, 125I-iodo-LSD and 125I- iodocyanopindolol. Secondly, we will establish second messenger linkages by examining the production (or inhibition) of cAMP and the hydrolysis of phospotidylinostitol. Finally, in assessing the role in development, we will further characterize an inhibitory growth factor, which is produced by our cultures in response to stimulation of their membrane serotonin receptors. We will also begin studies of co-cultures of astrocytes and serotonin neurons, to further elucidate this role.
