Nicotinic receptors co-localize with 5-HT(3) serotonin receptors on striatal nerve terminals

Nicotinic acetylcholine receptors and 5-HT₃ serotonin receptors are present on presynaptic nerve terminals in the striatum, where they have been shown to be involved in the regulation of dopamine release. Here, we explored the possibility that both receptor systems function on the same individual nerve terminals in the striatum, as assessed by confocal imaging of synaptosomes. On performing sequential stimulation, nicotine (500 nM) induced changes in [Ca²⁺]_i in most of the synaptosomes (80%) that had previously responded to stimulation with the 5-HT₃ receptor agonist m–chlorophenylbiguanide (mCPBG; 100 nM), whereas mCPBG induced [Ca²⁺]_i responses in approximately half of the synaptosomes that showed responses on nicotinic stimulation. The 5-HT₃ receptor–specific antagonist tropisetron blocked only the mCPBG–induced responses, but not the nicotinic responses on the same synaptosomes. Immunocytochemical staining revealed extensive co-localization of the 5-HT₃ receptor with the 4 nicotinic receptor subunit on the same synaptosomes, but not with the 3 and/or 5 subunits. Immunoprecipitation studies indicate that the 5-HT₃ receptor and the 4 nicotinic receptor subunit do not interact on the nerve terminals. The presence of nicotinic and 5-HT₃ receptors on the same presynaptic striatal nerve terminal indicates a convergence of cholinergic and serotonergic systems in the striatum.