Denis-Donini S
CNR Centre of Cytopharmacology, Milan, Italy.
Nature. 1989 Jun 29;339(6227):701-3. doi: 10.1038/339701a0.
In the olfactory bulb, tyrosine hydroxylase (TH), the rate-limiting enzyme in the biosynthesis of catecholamines, is expressed after birth when the axons of olfactory epithelial neurons have made synapses in the bulb. It has been suggested that expression of TH is regulated trans-synaptically because on deafferentation of the bulb there is a marked decrease in the contents of TH, dopamine and 3,4-dihydroxyphenylacetic acid, which, however, return to normal levels after regeneration of the primary afferents. To date the molecular signalling involved in this trans-synaptic induction has not yet been characterized; I have therefore studied the expression of dopaminergic properties (presence of TH and dopamine uptake) in dissociated cell cultures from embryonic mouse olfactory bulb. I report that the number of dopaminergic cells increases fivefold when olfactory bulb neurons are co-cultured with olfactory epithelial neurons and that soluble factors, rather than cell interactions, mediate this effect. The dopaminergic-inducing factor is the calcitonin gene-related peptide (CGRP) which is present in chemosensory neurons of the olfactory epithelium and when added at nanomolar concentrations to olfactory bulb cultures mimics the effect of olfactory epithelial neurons. Significantly the induction of dopaminergic phenotypes brought about by olfactory epithelial neurons is abolished by an antiserum to CGRP. These observations show that CGRP is involved in the differentiation of dopaminergic olfactory bulb neurons.
在嗅球中，酪氨酸羟化酶（TH）是儿茶酚胺生物合成中的限速酶，在出生后，当嗅觉上皮神经元的轴突在嗅球中形成突触时开始表达。有人提出，TH的表达是通过跨突触调节的，因为在嗅球去传入神经后，TH、多巴胺和3,4-二羟基苯乙酸的含量会显著下降，然而，在初级传入神经再生后，这些物质会恢复到正常水平。迄今为止，这种跨突触诱导所涉及的分子信号尚未得到表征；因此，我研究了来自胚胎小鼠嗅球的解离细胞培养物中多巴胺能特性（TH的存在和多巴胺摄取）的表达。我报告说，当嗅球神经元与嗅觉上皮神经元共培养时，多巴胺能细胞的数量增加了五倍，并且可溶性因子而非细胞间相互作用介导了这种效应。多巴胺能诱导因子是降钙素基因相关肽（CGRP），它存在于嗅觉上皮的化学感觉神经元中，当以纳摩尔浓度添加到嗅球培养物中时，可模拟嗅觉上皮神经元的作用。值得注意的是，抗CGRP血清可消除嗅觉上皮神经元对多巴胺能表型的诱导作用。这些观察结果表明，CGRP参与了多巴胺能嗅球神经元的分化。
