Nayak S V, Rondé P, Spier A D, Lummis S C, Nichols R A
Department of Pharmacology and Physiology, Medical College of Pennsylvania/Hahnemann University, Philadelphia, PA, USA.
Neuropharmacology. 2000 Oct;39(13):2681-90. doi: 10.1016/s0028-3908(00)00109-x.
Nicotinic acetylcholine receptors and 5-HT(3) 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 Ca(2+) in most of the synaptosomes ( approximately 80%) that had previously responded to stimulation with the 5-HT(3) receptor agonist m-chlorophenylbiguanide (mCPBG; 100 nM), whereas mCPBG induced Ca(2+) responses in approximately half of the synaptosomes that showed responses on nicotinic stimulation. The 5-HT(3) 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-HT(3) receptor with the alpha4 nicotinic receptor subunit on the same synaptosomes, but not with the alpha3 and/or alpha5 subunits. Immunoprecipitation studies indicate that the 5-HT(3) receptor and the alpha4 nicotinic receptor subunit do not interact on the nerve terminals. The presence of nicotinic and 5-HT(3) receptors on the same presynaptic striatal nerve terminal indicates a convergence of cholinergic and serotonergic systems in the striatum.
烟碱型乙酰胆碱受体和5-羟色胺（5-HT）3型血清素受体存在于纹状体的突触前神经末梢，研究表明它们参与多巴胺释放的调节。在此，我们通过对突触体进行共聚焦成像，探讨了这两种受体系统是否在纹状体中同一个体神经末梢上发挥作用。在进行序列刺激时，尼古丁（500 nM）可使大多数先前对5-HT3型受体激动剂间氯苯双胍（mCPBG；100 nM）刺激有反应的突触体（约80%）的细胞内钙离子浓度（[Ca(2+)]i）发生变化，而mCPBG可使约一半对烟碱刺激有反应的突触体产生[Ca(2+)]i反应。5-HT3型受体特异性拮抗剂托烷司琼仅阻断mCPBG诱导的反应，而不阻断同一突触体上的烟碱反应。免疫细胞化学染色显示，5-HT3型受体与α4烟碱受体亚基在同一突触体上广泛共定位，但与α3和/或α5亚基没有共定位。免疫沉淀研究表明，5-HT3型受体与α4烟碱受体亚基在神经末梢上不相互作用。同一突触前纹状体神经末梢上存在烟碱型和5-HT3型受体，表明纹状体中胆碱能和5-羟色胺能系统存在汇聚。
