Differential Mechanisms Involved in the Effect of Nicotinic Agonists DMPP and Lobeline to Release [3H]5-HT from Rat Hippocampal Slices

Abstract

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-β-erythroidine) on the release of [3H]5-HT from hippocampal slices. The nicotinic agonists DMPP and lobeline and electrical field stimulation, released [3H]5-HT from the hippocampus; other nicotinic agonists, such as (−)-nicotine, cytisine, and (−)-epibatidine had no effect. Unlike lobeline-induced release of [3H]5-HT, the effect of DMPP (10 and 40 μM) was antagonized by mecamylamine (20 and 10 μM). The effect of DMPP was [Ca2+]o-independent. In experiments carried out at 7°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 [3H]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. © 1997 Elsevier Science Ltd. All rights reserved.