SPECIFIC RECEPTORS FOR ALPHA-MELANOCYTE-STIMULATING HORMONE ARE WIDELY DISTRIBUTED IN TISSUES OF RODENTS
SPECIFIC RECEPTORS FOR ALPHA-MELANOCYTE-STIMULATING HORMONE ARE WIDELY DISTRIBUTED IN TISSUES OF RODENTS
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DOI：
10.1210/endo-121-5-1900
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发表时间：
1987-11-01
期刊：
影响因子：
4.8
通讯作者：
REICHLIN, S
中科院分区：
文献类型：
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作者：
TATRO, JB;REICHLIN, S
已知α-MSH作用于几种非黑素细胞类型，这导致了最近对其在发热、炎症、免疫和行为中的调节作用的兴趣。为了确定其可能的作用部位，我们研究了α-MSH受体在小鼠和大鼠各种组织中的分布。超强的和酶抗性的αMSH类似物Nle4，D-Phe7-αMSH(NDP-MSH)用乳过氧化物酶珠(Enzymobeads)进行放射性碘化，并用反相色谱纯化作为示踪剂。[125I]NDP-MSH与培养的小鼠黑色素瘤细胞B16和Cloudman S91显示出一致和特异的结合，这两种细胞对αMSH具有高度反应。根据其刺激B16细胞黑素生成的效力，该示踪剂具有完全的生物学活性。为了研究受体在体内的分布，将[125I]NDP-MSH静脉注射给C3H/HeJ(有色)小鼠和SD大鼠(白化)。为了确定组织摄取示踪剂的特异性，一些动物接受了大量摩尔过量的α-MSH和[125I]NDP-MSH。数据以组织与血浆的放射性浓度比表示。在小鼠中，在许多腺器官中发现了[125I]NDP-MSH的特异性(即可抑制MSH)结合，包括泪腺、Harderian、包皮、下颌下、肾上腺和胰腺，以及下颌下、肾上腺和胰腺，以及棕色和白色脂肪组织、膀胱、十二指肠、皮肤、脾和下丘脑。在大鼠身上，结果大体相似；在泪腺、哈德氏腺、包皮和甲状腺；胰腺、十二指肠、脾、下丘脑和白色脂肪组织中观察到特异性示踪剂摄取。这些结果表明，αMSH的特异性受体分布广泛，提示αMSH可能影响许多器官的功能。
.alpha.MSH is known to act on several nonmelanocyte cell types, which has led to recent interest in its regulatory roles in fever, inflammation, immunity, and behavior. To determine its possible sites of action, we examined the distribution of .alpha.MSH receptors in a variety of tissues in mice and rats. The superpotent and enzymatically resistant .alpha.MSH analog, Nle4,D-Phe7-.alpha.MSH (NDP-MSH), was radioiodinated using lactoperoxidase (Enzymobeads) and purified by reverse phase chromatography for use as a tracer. [125I]NDP-MSH exhibited consistent and specific binding to cultured B16 and Cloudman S91 murine melanoma cells, which are highly responsive to .alpha.MSH. The tracer had full biological activity, as determined by its potency in stimulating melanogenesis in B16 cells. To study receptor distribution in vivo, [125I]NDP-MSH was administered iv to C3H/HeJ (pigmented) mice and Sprague-Dawley (albino) rats. To determine the specificity of tracer uptake by tissues, some animals received a large molar excess of .alpha.MSH together with [125I]NDP-MSH. Data were expressed as tissue to plasma radioactivity concentration ratios. In mice, specific (i.e. .alpha.MSH-inhibitable) binding of [125I]NDP-MSH was found in a number of glandular organs, including lacrimal, Harderian, preputial, submandibular, and adrenal glands and pancreas, as well as in submandibular, and adrenal glands and pancreas, as well as in brown and white adipose tissues, bladder, duodenum, skin, spleen, and hypothalamus. In rats, results were generallysimilar; specific tracer uptake was observed in lacrimal, Harderian, preputial, and thyroid glands; pancreas, duodenum, spleen, hypothalamus; and white adipose tissue. These results show that specific receptors for .alpha.MSH are widely distributed, suggesting that .alpha.MSH may affect the functions of a number of organs.