{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T11:10:02Z","timestamp":1730373002724,"version":"3.28.0"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2000,11,1]],"date-time":"2000-11-01T00:00:00Z","timestamp":973036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Instillation of amlexanox, an anti-allergic drug, over a long period improves myopia in some allergy patients and in monkeys. The relaxing effect of amlexanox on persistent contraction of ciliary muscle may be involved in the improvement of myopia. In this study, the mechanism of the noncompetitive inhibition of carbachol-induced contractions by amlexanox (1\u2013100 \u03bcM) was investigated in isolated smooth muscle preparations of the rabbit ciliary body and guinea-pig taenia caecum.<\/jats:p>\n               <jats:p>In ciliary muscles, amlexanox (100 &amp;#x006e;\u0308m) inhibited both the phasic and tonic components of carbachol-induced contractions even in the presence of cyclopiazonic acid (10 &amp;#x006e;\u0308m) where the function of the sarcoplasmic reticulum was impaired, while diltiazem (3.2, 32\u03bcM) did not. In taenia caecum, diltiazem (3.2 \u03bcM) slightly inhibited the phasic component and abolished the tonic component of carbachol-induced contractions. Amlexanox also abolished the tonic component, but it did not decrease the 45Ca2+ uptake into taenia caecum smooth muscle cells induced by carbachol. Amlexanox did not increase the cyclic adenosine monophosphate (cyclicAMP) content of ciliary muscles in the presence of 3-isobutyl-1-methylxanthine (10 \u03bcm), while forskolin (1 \u03bcm) did. Gel-shift assay showed that the inhibition of carbachol-induced contractions by amlexanox was accompanied by a decrease in phosphorylation of the 20-kDa myosin light chain in taenia caecum tissue preparations. Amlexanox had no effect on calmodulin activity, whereas it inhibited phosphorylation of the myosin light chain by purified myosin light-chain kinase from chicken gizzard.<\/jats:p>\n               <jats:p>These results suggested that amlexanox may not affect either Ca2+ mobilization or calmodulin activity, although it inhibits myosin light-chain kinase, which may inhibit carbachol-induced contraction.<\/jats:p>","DOI":"10.1211\/0022357001777531","type":"journal-article","created":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T22:04:05Z","timestamp":1033509845000},"page":"1377-1385","source":"Crossref","is-referenced-by-count":1,"title":["Inhibitory Effects of Amlexanox on Carbachol-induced Contractions of Rabbit Ciliary Muscle and Guinea-pig Taenia Caecum"],"prefix":"10.1093","volume":"52","author":[{"given":"Noriko","family":"Watanabe","sequence":"first","affiliation":[{"name":"International R&D Division, Senju Pharmaceutical Co. Ltd , Osaka 541-0046,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukari","family":"Tominaga","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Department of Pharmacobiodynamics, Faculty of Pharmaceutical Sciences, Kanazawa University , Kanazawa 920-0934,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuya","family":"Mizutani","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Department of Pharmacobiodynamics, Faculty of Pharmaceutical Sciences, Kanazawa University , Kanazawa 920-0934,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Ogawa","sequence":"additional","affiliation":[{"name":"International R&D Division, Senju Pharmaceutical Co. Ltd , Osaka 541-0046,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromi","family":"Tsunobuchi-Ushijima","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Department of Pharmacobiodynamics, Faculty of Pharmaceutical Sciences, Kanazawa University , Kanazawa 920-0934,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuo","family":"Gomi","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Department of Pharmacobiodynamics, Faculty of Pharmaceutical Sciences, Kanazawa University , Kanazawa 920-0934,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2000,11,1]]},"reference":[{"key":"2024103110053565400_cit1","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1111\/j.1476-5381.1982.tb09353.x","article-title":"The binding properties of the muscarinic receptors of the cynomolgus monkey ciliary body and the response to the induction of agonist subsensitivity","volume":"77","author":"Barany","year":"1982","journal-title":"Br. 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Eye."},{"key":"2024103110053565400_cit19","first-page":"143","article-title":"Effect of amlexanox on myopic change in refractive error induced by carbachol instillation in monkeys (in Japanese)","volume":"16","author":"Watanabe","year":"1999","journal-title":"J. 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