Landis S C, Siegel R E, Schwab M
Department of Pharmacology, Case Western Reserve School of Medicine, Cleveland, Ohio 44106.
Dev Biol. 1988 Mar;126(1):129-40. doi: 10.1016/0012-1606(88)90246-1.
Previous studies of the cholinergic sympathetic innervation of rat sweat glands provide evidence for a change in neurotransmitter phenotype from noradrenergic to cholinergic during development. To define further the developmental history of cholinergic sympathetic neurons, we have used immunocytochemical techniques to examine developing and mature sweat gland innervation for the presence of the catecholamine synthetic enzymes tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) and for two neuropeptides present in the mature cholinergic innervation, vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP). In 7-day old animals, intensely TH- and DBH-immunoreactive axons were closely associated with the forming glands. The intensity of both the TH and DBH immunofluorescence decreased as the glands and their innervation developed. Neither TH-IR nor DBH-IR disappeared entirely; faint immunoreactivity for both enzymes was reproducibly detected in mature animals. In contrast to noradrenergic properties, the expression of peptide immunoreactivities appeared relatively late. No VIP-IR or CGRP-IR was detectable in the sweat gland innervation at 4 or 7 days. In some glands VIP-IR first appeared in axons at 10 days, and was evident in all glands by 14 days. CGRP-IR was detectable only after 14 days. In addition to VIP-IR and CGRP-IR, we examined the sweat gland innervation for several neuropeptides which have been described in noradrenergic sympathetic neurons including neuropeptide Y, somatostatin, substance P, and leu- and met-enkephalin; these peptides were not evident in either developing or mature sweat gland axons. Our observations provide further evidence for the early expression and subsequent modulation of noradrenergic properties in a population of cholinergic sympathetic neurons in vivo. In addition, the asynchronous appearance during development of the two neuropeptide immunoreactivities raises the possibility that the expression of peptide phenotypes may be controlled independently.
先前对大鼠汗腺胆碱能交感神经支配的研究表明，在发育过程中神经递质表型从去甲肾上腺素能转变为胆碱能。为了进一步明确胆碱能交感神经元的发育历程，我们运用免疫细胞化学技术，检测发育中和成熟的汗腺神经支配中儿茶酚胺合成酶酪氨酸羟化酶（TH）和多巴胺β-羟化酶（DBH）的存在情况，以及成熟胆碱能神经支配中存在的两种神经肽，即血管活性肠肽（VIP）和降钙素基因相关肽（CGRP）。在7日龄动物中，强烈的TH和DBH免疫反应性轴突与正在形成的腺体紧密相连。随着腺体及其神经支配的发育，TH和DBH免疫荧光的强度均降低。TH免疫反应性和DBH免疫反应性均未完全消失；在成熟动物中可重复检测到这两种酶的微弱免疫反应性。与去甲肾上腺素能特性不同，肽免疫反应性的表达出现相对较晚。在4天或7天时，在汗腺神经支配中未检测到VIP免疫反应性或CGRP免疫反应性。在一些腺体中，VIP免疫反应性在10天时首次出现在轴突中，到14天时在所有腺体中都很明显。CGRP免疫反应性仅在14天后才可检测到。除了VIP免疫反应性和CGRP免疫反应性外，我们还检测了汗腺神经支配中几种在去甲肾上腺素能交感神经元中已被描述的神经肽，包括神经肽Y、生长抑素、P物质以及亮氨酸脑啡肽和甲硫氨酸脑啡肽；这些肽在发育中的或成熟的汗腺轴突中均不明显。我们的观察结果为体内胆碱能交感神经元群体中去甲肾上腺素能特性的早期表达及随后的调节提供了进一步的证据。此外，两种神经肽免疫反应性在发育过程中的异步出现增加了肽表型表达可能独立控制的可能性。
