Hydroxychloroquine therapy in patients with primary Sjögren's syndrome may improve salivary gland hypofunction by inhibition of glandular cholinesterase
To determine whether (i) cholinesterase activity is increased in the saliva of patients with primary Sjogren's syndrome (pSS), (ii) increased levels of cholinesterase of lymphocyte origin could interfere with the secretory activity of submandibular acinar cells, and (iii) hydroxychloroquine at...
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Veröffentlicht in: | British journal of rheumatology 2005-04, Vol.44 (4), p.449-455 |
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description | To determine whether (i) cholinesterase activity is increased in the saliva of patients with primary Sjogren's syndrome (pSS), (ii) increased levels of cholinesterase of lymphocyte origin could interfere with the secretory activity of submandibular acinar cells, and (iii) hydroxychloroquine at therapeutic doses could interfere with cholinesterase activity.
The Ellman method was used to determine the levels of salivary cholinesterase activity and the K(i) of both chloroquine and hydroxychloroquine for serum cholinesterase. The ability of lymphocyte cholinesterase to inhibit the acetylcholine (ACh)-evoked rise in [Ca(2+)](i) in mouse submandibular acinar cells was determined using fura-2 microfluorimetry.
Patients with pSS had significantly higher levels of cholinesterase activity in both their unstimulated (P < 0.05) and stimulated saliva (P < 0.0001) compared with control subjects. Lymphocyte cholinesterase was capable of inhibiting the ACh-evoked rise in [Ca(2+)](i). The in vitro K(i) for hydroxychloroquine inhibition of cholinesterase was 0.38 +/- 1.4 microM.
These data suggest that increased levels of cholinesterase present in the salivary glands of patients with pSS may contribute to glandular hypofunction and provide evidence that the therapeutic enhancement of salivary secretion in patients with pSS by hydroxychloroquine may be mediated by inhibition of glandular cholinesterase activity, although further in vivo investigation is needed. |
doi_str_mv | 10.1093/rheumatology/keh506 |
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The Ellman method was used to determine the levels of salivary cholinesterase activity and the K(i) of both chloroquine and hydroxychloroquine for serum cholinesterase. The ability of lymphocyte cholinesterase to inhibit the acetylcholine (ACh)-evoked rise in [Ca(2+)](i) in mouse submandibular acinar cells was determined using fura-2 microfluorimetry.
Patients with pSS had significantly higher levels of cholinesterase activity in both their unstimulated (P < 0.05) and stimulated saliva (P < 0.0001) compared with control subjects. Lymphocyte cholinesterase was capable of inhibiting the ACh-evoked rise in [Ca(2+)](i). The in vitro K(i) for hydroxychloroquine inhibition of cholinesterase was 0.38 +/- 1.4 microM.
These data suggest that increased levels of cholinesterase present in the salivary glands of patients with pSS may contribute to glandular hypofunction and provide evidence that the therapeutic enhancement of salivary secretion in patients with pSS by hydroxychloroquine may be mediated by inhibition of glandular cholinesterase activity, although further in vivo investigation is needed.</description><identifier>ISSN: 1462-0324</identifier><identifier>ISSN: 1460-2172</identifier><identifier>EISSN: 1462-0332</identifier><identifier>EISSN: 1460-2172</identifier><identifier>DOI: 10.1093/rheumatology/keh506</identifier><identifier>PMID: 15590764</identifier><identifier>CODEN: BJRHDF</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Animals ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiparasitic agents ; Biological and medical sciences ; Bones, joints and connective tissue. Antiinflammatory agents ; Butyrylcholinesterase - metabolism ; Cholinesterase Inhibitors - pharmacology ; Cholinesterase Inhibitors - therapeutic use ; Cholinesterases - metabolism ; Dose-Response Relationship, Drug ; Female ; Humans ; Hydroxychloroquine - pharmacology ; Hydroxychloroquine - therapeutic use ; Lymphocyte Activation ; Male ; Medical sciences ; Mice ; Middle Aged ; Pharmacology. Drug treatments ; Saliva - enzymology ; Salivary Glands - drug effects ; Salivary Glands - enzymology ; Salivation ; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis ; Sjogren's Syndrome - drug therapy ; Sjogren's Syndrome - enzymology ; Sjogren's Syndrome - physiopathology ; T-Lymphocytes - enzymology</subject><ispartof>British journal of rheumatology, 2005-04, Vol.44 (4), p.449-455</ispartof><rights>2005 INIST-CNRS</rights><rights>Copyright Oxford University Press(England) Apr 2005</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c360t-81940f3839b1b647a45b756a8ab696808f6a4ac2c213737241b60a0a058e7bba3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16714145$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15590764$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>DAWSON, L. J</creatorcontrib><creatorcontrib>CAULFIELD, V. L</creatorcontrib><creatorcontrib>STANBURY, J. B</creatorcontrib><creatorcontrib>FIELD, A. E</creatorcontrib><creatorcontrib>CHRISTMAS, S. E</creatorcontrib><creatorcontrib>SMITH, P. M</creatorcontrib><title>Hydroxychloroquine therapy in patients with primary Sjögren's syndrome may improve salivary gland hypofunction by inhibition of glandular cholinesterase</title><title>British journal of rheumatology</title><addtitle>Rheumatology (Oxford)</addtitle><description>To determine whether (i) cholinesterase activity is increased in the saliva of patients with primary Sjogren's syndrome (pSS), (ii) increased levels of cholinesterase of lymphocyte origin could interfere with the secretory activity of submandibular acinar cells, and (iii) hydroxychloroquine at therapeutic doses could interfere with cholinesterase activity.
The Ellman method was used to determine the levels of salivary cholinesterase activity and the K(i) of both chloroquine and hydroxychloroquine for serum cholinesterase. The ability of lymphocyte cholinesterase to inhibit the acetylcholine (ACh)-evoked rise in [Ca(2+)](i) in mouse submandibular acinar cells was determined using fura-2 microfluorimetry.
Patients with pSS had significantly higher levels of cholinesterase activity in both their unstimulated (P < 0.05) and stimulated saliva (P < 0.0001) compared with control subjects. Lymphocyte cholinesterase was capable of inhibiting the ACh-evoked rise in [Ca(2+)](i). The in vitro K(i) for hydroxychloroquine inhibition of cholinesterase was 0.38 +/- 1.4 microM.
These data suggest that increased levels of cholinesterase present in the salivary glands of patients with pSS may contribute to glandular hypofunction and provide evidence that the therapeutic enhancement of salivary secretion in patients with pSS by hydroxychloroquine may be mediated by inhibition of glandular cholinesterase activity, although further in vivo investigation is needed.</description><subject>Animals</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiparasitic agents</subject><subject>Biological and medical sciences</subject><subject>Bones, joints and connective tissue. Antiinflammatory agents</subject><subject>Butyrylcholinesterase - metabolism</subject><subject>Cholinesterase Inhibitors - pharmacology</subject><subject>Cholinesterase Inhibitors - therapeutic use</subject><subject>Cholinesterases - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Humans</subject><subject>Hydroxychloroquine - pharmacology</subject><subject>Hydroxychloroquine - therapeutic use</subject><subject>Lymphocyte Activation</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Middle Aged</subject><subject>Pharmacology. Drug treatments</subject><subject>Saliva - enzymology</subject><subject>Salivary Glands - drug effects</subject><subject>Salivary Glands - enzymology</subject><subject>Salivation</subject><subject>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</subject><subject>Sjogren's Syndrome - drug therapy</subject><subject>Sjogren's Syndrome - enzymology</subject><subject>Sjogren's Syndrome - physiopathology</subject><subject>T-Lymphocytes - enzymology</subject><issn>1462-0324</issn><issn>1460-2172</issn><issn>1462-0332</issn><issn>1460-2172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU9u1DAYxS0EoqVwAiRkIQGroXb8L1lWFaVIlVgA6-izx5l4cOxgJ4UcpRfhAlwMDxNRhLywLf3ee5_9EHpOyVtKGnaeejsPMEUfd8v5V9sLIh-gU8pltSGMVQ__nit-gp7kvCeECMrqx-iECtEQJfkpurtetin-WEzvY4rfZhcsnnqbYFywC3iEydkwZfzdTT0ekxsgLfjT_tfPXbLhTcZ5CUU_WDxAEQxjircWZ_Du9gDuPIQt7pcxdnMwk4sB64Nv77T7c4vdkZk9JGz66Et-nkp8tk_Row58ts_W_Qx9uXr3-fJ6c_Px_YfLi5uNYZJMm5o2nHSsZo2mWnIFXGglJNSgZSNrUncSOJjKVJQppipeKAJlidoqrYGdoddH3_Hw_pLeDi4b68tYNs65lUpUiqumgC__A_dxTqHM1tJGyJpRyQvEjpBJMedku3b9tJaS9lBb-29t7bG2onqxWs96sNt7zdpTAV6tAGQDvksQjMv3nFSUUy7Yb6nnqjE</recordid><startdate>20050401</startdate><enddate>20050401</enddate><creator>DAWSON, L. 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M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c360t-81940f3839b1b647a45b756a8ab696808f6a4ac2c213737241b60a0a058e7bba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiparasitic agents</topic><topic>Biological and medical sciences</topic><topic>Bones, joints and connective tissue. Antiinflammatory agents</topic><topic>Butyrylcholinesterase - metabolism</topic><topic>Cholinesterase Inhibitors - pharmacology</topic><topic>Cholinesterase Inhibitors - therapeutic use</topic><topic>Cholinesterases - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Humans</topic><topic>Hydroxychloroquine - pharmacology</topic><topic>Hydroxychloroquine - therapeutic use</topic><topic>Lymphocyte Activation</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Middle Aged</topic><topic>Pharmacology. Drug treatments</topic><topic>Saliva - enzymology</topic><topic>Salivary Glands - drug effects</topic><topic>Salivary Glands - enzymology</topic><topic>Salivation</topic><topic>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</topic><topic>Sjogren's Syndrome - drug therapy</topic><topic>Sjogren's Syndrome - enzymology</topic><topic>Sjogren's Syndrome - physiopathology</topic><topic>T-Lymphocytes - enzymology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>DAWSON, L. J</creatorcontrib><creatorcontrib>CAULFIELD, V. L</creatorcontrib><creatorcontrib>STANBURY, J. B</creatorcontrib><creatorcontrib>FIELD, A. E</creatorcontrib><creatorcontrib>CHRISTMAS, S. E</creatorcontrib><creatorcontrib>SMITH, P. M</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of rheumatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>DAWSON, L. J</au><au>CAULFIELD, V. L</au><au>STANBURY, J. B</au><au>FIELD, A. E</au><au>CHRISTMAS, S. E</au><au>SMITH, P. M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hydroxychloroquine therapy in patients with primary Sjögren's syndrome may improve salivary gland hypofunction by inhibition of glandular cholinesterase</atitle><jtitle>British journal of rheumatology</jtitle><addtitle>Rheumatology (Oxford)</addtitle><date>2005-04-01</date><risdate>2005</risdate><volume>44</volume><issue>4</issue><spage>449</spage><epage>455</epage><pages>449-455</pages><issn>1462-0324</issn><issn>1460-2172</issn><eissn>1462-0332</eissn><eissn>1460-2172</eissn><coden>BJRHDF</coden><abstract>To determine whether (i) cholinesterase activity is increased in the saliva of patients with primary Sjogren's syndrome (pSS), (ii) increased levels of cholinesterase of lymphocyte origin could interfere with the secretory activity of submandibular acinar cells, and (iii) hydroxychloroquine at therapeutic doses could interfere with cholinesterase activity.
The Ellman method was used to determine the levels of salivary cholinesterase activity and the K(i) of both chloroquine and hydroxychloroquine for serum cholinesterase. The ability of lymphocyte cholinesterase to inhibit the acetylcholine (ACh)-evoked rise in [Ca(2+)](i) in mouse submandibular acinar cells was determined using fura-2 microfluorimetry.
Patients with pSS had significantly higher levels of cholinesterase activity in both their unstimulated (P < 0.05) and stimulated saliva (P < 0.0001) compared with control subjects. Lymphocyte cholinesterase was capable of inhibiting the ACh-evoked rise in [Ca(2+)](i). The in vitro K(i) for hydroxychloroquine inhibition of cholinesterase was 0.38 +/- 1.4 microM.
These data suggest that increased levels of cholinesterase present in the salivary glands of patients with pSS may contribute to glandular hypofunction and provide evidence that the therapeutic enhancement of salivary secretion in patients with pSS by hydroxychloroquine may be mediated by inhibition of glandular cholinesterase activity, although further in vivo investigation is needed.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>15590764</pmid><doi>10.1093/rheumatology/keh506</doi><tpages>7</tpages></addata></record> |
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subjects | Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antiparasitic agents Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Butyrylcholinesterase - metabolism Cholinesterase Inhibitors - pharmacology Cholinesterase Inhibitors - therapeutic use Cholinesterases - metabolism Dose-Response Relationship, Drug Female Humans Hydroxychloroquine - pharmacology Hydroxychloroquine - therapeutic use Lymphocyte Activation Male Medical sciences Mice Middle Aged Pharmacology. Drug treatments Saliva - enzymology Salivary Glands - drug effects Salivary Glands - enzymology Salivation Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis Sjogren's Syndrome - drug therapy Sjogren's Syndrome - enzymology Sjogren's Syndrome - physiopathology T-Lymphocytes - enzymology |
title | Hydroxychloroquine therapy in patients with primary Sjögren's syndrome may improve salivary gland hypofunction by inhibition of glandular cholinesterase |
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