Differential mechanisms involved in the effect of nicotinic agonists DMPP and lobeline to release [H-3]5-HT from rat hippocampal slices

In the present study we investigated the effect of different nicotinic agonists (dimethylphenylpiperazinium-iodide (DMPP), (-)nicotine, cytisine, (-)-lobeline, and (-)epibatidine) and antagonists (mecamylamine and dihydro-beta-erythroidine) on the release of [H-3]5-HT from hippocampal slices. The nicotinic agonists DMPP and lobeline and electrical field stimulation, released [H-3]5-HT from the hippocampus; other nicotinic agonists, such as (-)-nicotine, cytisine, and (-)-epibatidine had no effect. Unlike lobeline-induced release of [H-3]5-HT, the effect of DMPP (10 and 40 mu M) was antagonized by mecamylamine (20 and 10 mu M). The effect of DMPP was [Ca2+](o)-independent. In experiments carried out at 7 degrees C, i.e. the membrane carrier proteins are inhibited and the release by lobeline was abolished while the DMPP-induced release of 5-HT was rather potentiated. It is proposed that the effect of DMPP and lobeline, to enhance the release of [H-3]5-HT from the hippocampus, was mediated by two different mechanisms. While DMPP-induced 5-HT release can be linked to a non-classical nAChR activation ([Ca2+](o)-independence), the effect of lobeline was likely mediated by uptake carriers. (C) 1997 Elsevier Science Ltd.