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

Research Project

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 *help	¥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.