Finley J C, Polak J, Katz D M
Department of Medicine, University Hospitals of Cleveland, OH.
Neuroscience. 1992 Dec;51(4):973-87. doi: 10.1016/0306-4522(92)90534-9.
Hypoxic stimulation of carotid body chemoreceptors is conveyed to the brainstem by primary sensory neurons whose peripheral axons run in the carotid sinus nerve. While considerable attention has focused on defining chemical neuroregulators released by glomus cells in the carotid body, our understanding of the morphology, distribution and transmitter phenotype of these carotid body afferent neurons remains limited. Carotid body afferent neurons were labeled by microinjection of the retrograde tracer, Fluorogold, into the vascularly isolated rat carotid body. In addition, immunoelectron microscopy was used to correlate transmitter phenotype with ultrastructural features of afferent terminals in the carotid body. Our results indicate that 41% of all carotid body afferent neurons express tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, whereas 7% contain substance P. Tyrosine hydroxylase- and substance P-positive neurons constitute separate subpopulations of carotid body afferents, as these two phenotypes were not colocalized. Most of the tyrosine hydroxylase-containing carotid body afferent neurons were small- or medium-sized (mean cell diameter 15-20 microns) and located in the distal petrosal ganglion, whereas the majority of substance P-containing carotid body afferent neurons were medium- to large-sized (mean cell diameter 20-29 microns) and located in the proximal petrosal ganglion and jugular ganglion. These differences strengthen the notion that these catecholaminergic and peptidergic carotid body afferent neurons give rise to functionally distinct subsets of chemoafferent fibers. To further characterize the catecholaminergic phenotype expressed by tyrosine hydroxylase-positive cells in the petrosal ganglion, we examined the colocalization of tyrosine hydroxylase and DOPA decarboxylase, the dopamine-synthesizing enzyme. Eighty-six per cent of tyrosine hydroxylase-positive neurons in the distal petrosal ganglion also contained DOPA decarboxylase; as these cells do not express the norepinephrine-synthesizing enzyme, dopamine beta-hydroxylase, these data indicate that the catecholaminergic carotid body afferent neurons are dopaminergic. Finally, ultrastructural analysis of the peripheral processes of tyrosine hydroxylase-positive afferent terminals in the carotid body demonstrated endings in close opposition to Type I glomus cells, consistent with a role for dopaminergic afferent neurons in carotid body chemoreception. One possibility is that these cells, in addition to their role as afferents, constitute a morphologic substrate for dopaminergic "efferent" inhibition in the carotid body.
颈动脉体化学感受器的缺氧刺激由初级感觉神经元传递至脑干，这些神经元的外周轴突走行于颈动脉窦神经中。尽管相当多的注意力集中在确定颈动脉体中球细胞释放的化学神经调节剂上，但我们对这些颈动脉体传入神经元的形态、分布和递质表型的了解仍然有限。通过将逆行示踪剂荧光金微量注射到血管分离的大鼠颈动脉体中，标记颈动脉体传入神经元。此外，免疫电子显微镜用于将递质表型与颈动脉体传入终末的超微结构特征相关联。我们的结果表明，所有颈动脉体传入神经元中有41%表达酪氨酸羟化酶，这是儿茶酚胺生物合成中的限速酶，而7%含有P物质。酪氨酸羟化酶阳性和P物质阳性神经元构成颈动脉体传入神经元的不同亚群，因为这两种表型不共定位。大多数含酪氨酸羟化酶的颈动脉体传入神经元为小或中型（平均细胞直径15 - 20微米），位于岩神经节远端，而大多数含P物质的颈动脉体传入神经元为中到大型（平均细胞直径20 - 29微米），位于岩神经节近端和颈静脉神经节。这些差异强化了这样一种观点，即这些儿茶酚胺能和肽能的颈动脉体传入神经元产生功能上不同的化学传入纤维亚群。为了进一步表征岩神经节中酪氨酸羟化酶阳性细胞所表达的儿茶酚胺能表型，我们检测了酪氨酸羟化酶和多巴胺合成酶多巴脱羧酶的共定位情况。岩神经节远端86%的酪氨酸羟化酶阳性神经元也含有多巴脱羧酶；由于这些细胞不表达去甲肾上腺素合成酶多巴胺β-羟化酶，这些数据表明儿茶酚胺能颈动脉体传入神经元是多巴胺能的。最后，对颈动脉体中酪氨酸羟化酶阳性传入终末外周突起的超微结构分析显示，其终末与I型球细胞紧密相对，这与多巴胺能传入神经元在颈动脉体化学感受中的作用一致。一种可能性是，这些细胞除了作为传入神经元的作用外，还构成了颈动脉体中多巴胺能“传出”抑制的形态学基础。
