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
Hauptverfasser: DAWSON, L. J, CAULFIELD, V. L, STANBURY, J. B, FIELD, A. E, CHRISTMAS, S. E, SMITH, P. M
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container_end_page 455
container_issue 4
container_start_page 449
container_title British journal of rheumatology
container_volume 44
creator DAWSON, L. J
CAULFIELD, V. L
STANBURY, J. B
FIELD, A. E
CHRISTMAS, S. E
SMITH, P. M
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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J ; CAULFIELD, V. L ; STANBURY, J. B ; FIELD, A. E ; CHRISTMAS, S. E ; SMITH, P. M</creator><creatorcontrib>DAWSON, L. J ; CAULFIELD, V. L ; STANBURY, J. B ; FIELD, A. E ; CHRISTMAS, S. E ; SMITH, P. M</creatorcontrib><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 &lt; 0.05) and stimulated saliva (P &lt; 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. 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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. 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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. 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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. 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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 &lt; 0.05) and stimulated saliva (P &lt; 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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source Oxford University Press Journals All Titles (1996-Current); MEDLINE; Alma/SFX Local Collection
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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