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

• Project/Area Number: 13671861
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: KYUSHU UNIVERSITY OF HEALTH AND WELFARE
• Principal Investigator: YAMAMOTO Ryuichi PARMA CEUTICAL SCIENCES PROFESSOR, 薬学部, 教授 (10094111)
• Co-Investigator(Kenkyū-buntansha): SAWADA Atsushi HEALTH SCIENCES PROFESSOR, 保健科学部, 教授 (10040247) ; ASADA Yujiro MIYAZAKI MEDICAL COLLEGE PROFESSOR, 医学部, 教授 (70202588) ; NAO-I Nobuhisa MIYAZAKI MEDICAL COLLEGE PROFESSOR, 医学部, 教授 (50211412) ; OKANO Mayumi HEALTH SCIENCES LECTURER, 保健科学部, 講師 (80320498)
• Project Period (FY): 2001 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000); Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: 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

Research Abstract

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.

Research Products

• [Publications] 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)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 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. 132. 1455-1466 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 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- terminal 12 peptide in bovine adrenal chromaffin cells"Molecular Brain Research. 87. 175-183 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Seiji Shiraishi, Izumi Shibuya, Yasuhito, Uezono, Hiroki Yokoo, Yumiko Toyohira, Ryuichi Yamamoto, Toshihiko Yanagita, Hideyuki Kobayashi and Akihiko Wada: "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. 132. 1455-1466 (2001)
  • Description: 「研究成果報告書概要(欧文)」より