{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T07:50:40Z","timestamp":1767858640754,"version":"3.49.0"},"reference-count":32,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,2,17]],"date-time":"2009-02-17T00:00:00Z","timestamp":1234828800000},"content-version":"vor","delay-in-days":1539,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2004,12]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Nitric oxide is an intracellular and diffusible messenger of neurotransmitters involved in salivary secretion, as well as an inflammatory mediator in salivary gland diseases. It is synthesized by three different isoforms of nitric oxide synthase (NOS), each subject to a fine transcriptional, post\u2010transcriptional and\/or post\u2010translational regulation. Our purpose was to study the possible mechanisms leading to NOS downregulation in submandibular glands of normal mice and in the nonobese diabetic (NOD) mouse model of salivary dysfunction with lower NOS activity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>NOS activity and cGMP accumulation were determined by radioassays in submandibular glands of both mice in the presence of the protein kinase inhibitors KN\u201093 and bisindolylmaleimide. NOS I mRNA and protein expression and localization were assessed by RT\u2013PCR, Western blot and immunohistochemistry.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>A downregulatory effect of calcium\u2013calmodulin kinase II (CaMK II) on NOS activity in submandibular glands of both NOD and BALB\/c mice was observed. Our results are consistent with a physiological regulation of NOS activity by this kinase but not by PKC in normal BALB\/c mice. They are also supportive of a role for CaMK II in the lack of detectable NOS activity in submandibular glands of NOD mice. KN\u201093 also restored cGMP accumulation in NOD submandibular glands.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The downregulation of NOS in NOD mice seems to be mainly mediated by this kinase rather than the result of a lower expression or different cellular localization of the enzyme. It was not related to different substrate or cofactors availability either.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2004) <jats:bold>143<\/jats:bold>, 1058\u20131065. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705952\">10.1038\/sj.bjp.0705952<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705952","type":"journal-article","created":{"date-parts":[[2004,11,9]],"date-time":"2004-11-09T01:14:38Z","timestamp":1099962878000},"page":"1058-1065","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Inhibition of calcium\u2010calmodulin kinase restores nitric oxide production and signaling in submandibular glands of a mouse model of salivary dysfunction"],"prefix":"10.1111","volume":"143","author":[{"given":"Florencia","family":"Rosignoli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Roca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Meiss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicol\u00e1s","family":"Pregi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia P\u00e9rez","family":"Leir\u00f3s","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3570593"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.00705.x"},{"key":"e_1_2_7_4_1","first-page":"10976","article-title":"Nitric oxide synthase regulatory sites","volume":"267","author":"BREDT D.S.","year":"1992","journal-title":"J. Biol. Chem."},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.2.682"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4160(96)90091-3"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(02)00049-4"},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1096\/fasebj.12.10.773","article-title":"Expressional control of the constitutive isoforms of nitric oxide synthase (NOS I and NOS III)","volume":"12","author":"F\u00d6RSTERMANN U.","year":"1998","journal-title":"FASEB J."},{"key":"e_1_2_7_9_1","first-page":"15","article-title":"Approaches to the treatment of Sj\u00f6gren's syndrome","volume":"27","author":"FOX R.I.","year":"2000","journal-title":"J. Rheumatol."},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.29.20597"},{"key":"e_1_2_7_11_1","first-page":"G433","article-title":"Down\u2010regulation of \u03b2\u2010adrenergic receptors and signal transduction response in salivary glands of NOD mice","volume":"266","author":"HU Y.","year":"1994","journal-title":"Am. J. Physiol."},{"key":"e_1_2_7_12_1","first-page":"46","article-title":"Epidemiology of Sj\u00f6gren's syndrome","volume":"24","author":"JACOBSSON L.T.H.","year":"1995","journal-title":"Rheumatol. Europe"},{"key":"e_1_2_7_13_1","first-page":"675","article-title":"Inappropriate apoptosis of salivary and lacrimal gland epithelium of immunodeficient NOD\u2010scid mice","volume":"16","author":"KONG L.","year":"1998","journal-title":"Clin. Exp. Rheumatol."},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780400515"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000026342"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1042\/0264-6021:3550087"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(05)81351-8"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119782"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)36703-0"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200209000-00007"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01827430"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-1838(99)00102-2"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.11.5767"},{"key":"e_1_2_7_24_1","first-page":"367","volume-title":"Immunology","author":"ROITT I.M.","year":"1998"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1006\/clim.2001.5097"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(02)01375-4"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(02)00223-0"},{"issue":"1","key":"e_1_2_7_28_1","first-page":"S15","article-title":"Deficient VIP activated signaling and secretion in salivary glands of NOD mice","author":"ROSIGNOLI F.","year":"2003","journal-title":"Clin. Immunol."},{"key":"e_1_2_7_29_1","first-page":"212","article-title":"Advances in the diagnosis and concept of Sj\u00f6gren's syndrome (autoimmune exocrinopathy)","volume":"92","author":"STRAND V.","year":"1980","journal-title":"Bull. Rheum. Dis."},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1006\/clim.2002.5189"},{"key":"e_1_2_7_31_1","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1096\/fasebj.11.11.9285482","article-title":"Calmodulin\u2010dependent protein kinase II mediates signal transduction in apoptosis","volume":"11","author":"WRIGHT S.C.","year":"1997","journal-title":"FASEB J."},{"key":"e_1_2_7_32_1","first-page":"2371","article-title":"Excessive synthesis of matrix metalloproteinases in exocrine tissues of NOD mouse models for Sj\u00f6gren's syndrome","volume":"25","author":"YAMACHIKA S.","year":"1998","journal-title":"J. Rheumatol."},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200316326"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0705952","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0705952","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0705952","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T00:14:37Z","timestamp":1697242477000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0705952"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,12]]},"references-count":32,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2004,12]]}},"alternative-id":["10.1038\/sj.bjp.0705952"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0705952","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,12]]},"assertion":[{"value":"2009-02-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}