A new mechanism for the fine adjustment of pupil size : Relation with endogenous peptide

瞳孔大小微调的新机制：与内源性肽的关系

• 批准号: 13671861
• 负责人: YAMAMOTO Ryuichi
• 金额: $ 2.24万
• 依托单位: KYUSHU UNIVERSITY OF HEALTH AND WELFARE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671861/
• 关键词: regulation of pupil size; iris sphincter muscle; smooth muscle; peptide; adrenomedullin; receptor; signal transduction; nitric oxide; 瞳孔括約筋; アドレノメヂュリン; 細胞内情報伝達系

Two types of antagonistic muscles, the sphincter and the dilator ones, regulate the pupil size. This iris sphincter muscle is organized in a circular band with parasympathetic innervation which, when stimulated, causes miosis. On the other hand, the iris dilator muscle is oriented radially and innervated by the sympathetic nerves which, when stimulated, causes mydriasis. Mechanisms for the fine adjustment of the iris sphincter muscle tone are largely unknown. Our results demonstrate for the first time that in the isolated bovine iris sphincter muscle, adrenomedullin (AM) decreases resting tension of the muscle in an autocrine and paracrine manner. Its biological effects may be due to direct involvement of AM receptors, and also to stimulation of CGRP_1-receotirs. Stimulation of these receptors by the peptide lead to the activation of adenylate cyclase and soluble guanylate cyclase and subsequent relaxation of the muscle strip. We also found that proadrenomedullin N-terminal 12 peptide selectively inhibited the nicotinic cholinergic receptors. Furthermore, we found that the increase in cytoplasmic Ca^<2+> induced down-regulation of cell surface Na^+ chanel.

两种类型的拮抗肌，括约肌和扩张肌，调节瞳孔的大小。这虹膜括约肌组织在一个环形带与副交感神经支配，当刺激，导致瞳孔缩小。另一方面，虹膜扩张肌呈放射状，受交感神经支配，当受到刺激时，会引起瞳孔放大。虹膜括约肌张力的精细调节机制在很大程度上是未知的。我们的研究结果首次表明，在离体牛虹膜括约肌，肾上腺髓质素（AM）降低肌肉的自分泌和旁分泌方式的静息张力。其生物学作用可能与AM受体直接参与有关，也可能与刺激CGRP_1受体有关。肽对这些受体的刺激导致腺苷酸环化酶和可溶性鸟苷酸环化酶的激活以及随后肌肉条的松弛。我们还发现肾上腺髓质素前体N端12肽选择性抑制烟碱胆碱能受体。此外，我们还发现胞浆Ca^<2+>的增加可引起细胞表面Na^+通道的下调。

项目成果

Kobayashi H., Shiraishi S., Yanagita T., Yokoo H., Yamamoto R., et al.: "The Chromaffin Cell"Annals of the New York Akademy of Sciences. 134 (2002)

Kobayashi H.、Shiraishi S.、Yanagita T.、Yokoo H.、Yamamoto R.等人：纽约科学院年鉴《嗜铬细胞》。

Shiraishi S., Shibuya I., Yokoo H., Toyohira Y., Yamamoto R.et al.: "Heterogeneous increases of cytoplasmic calcium: distinct effects on down-regulation of cell surface sodium channels and sodium channel subunit mRNA levels"British Journal of Pharmacology

Shiraishi S.、Shibuya I.、Yokoo H.、Toyohira Y.、Yamamoto R.等人：“细胞质钙的异质增加：对细胞表面钠通道和钠通道亚基 mRNA 水平下调的独特影响”英国杂志

Kobayashi H., Yamamoto R.et al.: "Selective inhibition of nicotinic cholinergic receptors by proadrenomedullin N-terminal 12 peptide in bovine adrenal chromaffin cells"Molecular Brain Research. 87. 175-183 (2001)

Kobayashi H.、Yamamoto R.等人：“牛肾上腺嗜铬细胞中肾上腺髓质素原 N 末端 12 肽对烟碱胆碱能受体的选择性抑制”分子脑研究。

Hideyuki Kobayashi, Ryuichi Yamamoto, Kazuo Kitamura, Kenji Kuwasako, Shin-ichi, Minami, Toshihiko Yanagita, Seiji Shiraishi, Hiroki Yokoo, Tanenao Eto and Akihiko Wada: "Selective inhibition of nicotinic cholinergic receptors by proadrenomedullin N- term

Hideyuki Kobayashi、Ryuichi Yamamoto、Kazuo Kitamura、Kenji Kuwasako、Shin-ichi、Minami、Toshihiko Yanagita、Seiji Shiraishi、Hiroki Yokoo、Tanenao Eto 和 Akihiko Wada：“前肾上腺髓质素 N-term 对烟碱胆碱能受体的选择性抑制