Elsevier

Clinical Immunology

Volume 101, Issue 3, December 2001, Pages 249-263
Clinical Immunology

Short Analytical Review
Use of Muscarinic Agonists in the Treatment of Sjögren's Syndrome

https://doi.org/10.1006/clim.2001.5128Get rights and content

Abstract

Two muscarinic agonists (pilocarpine and cevimeline) have recently been approved for the treatment of symptoms of xerostomia in Sjögren's syndrome (SS). These agents stimulate the M1 and M3 receptors present on salivary glands, leading to increased secretory function. The use of these agents emphasizes the importance of neuroendocrine mechanisms in SS, which is considered an autoimmune disorder. We review recent studies on the release of cytokines and metalloproteinases in SS-affected glands and their influence on the release of and response to neurotransmitters. Also, we review the structure and function of muscarinic receptors as they may relate to SS and the potential use of novel muscarinic agonists in SS.

References (165)

  • D. Gurwitz et al.

    Discrete activation of transduction pathways associated with acetylcholine m1 receptor by several muscarinic ligands

    Eur. J. Pharmacol.

    (1994)
  • Y. Ishikawa et al.

    Aquaporin water channel in salivary glands

    Jpn. J. Pharmacol.

    (2000)
  • Y. Ishikawa et al.

    Persistent increase in the amount of aquaporin-5 in the apical plasma membrane of rat parotid acinar cells induced by a muscarinic agonist SNI-2011

    FEBS Lett.

    (2000)
  • C. Main et al.

    Human recombinant interleukin 1 beta suppresses acetylcholine release from rat myenteric plexus

    Gastroenterology

    (1993)
  • I.L. Campbell

    Neuropathogenic actions of cytokines assessed in transgenic mice

    Int. J. Dev. Neurosci.

    (1995)
  • G. Lu et al.

    Tumor necrosis factor-alpha and interleukin-1 induce activation of MAP kinase and SAP kinase in human neuroma fibroblasts

    Neurochem. Int.

    (1997)
  • M. Balaram et al.

    Efficacy and tolerability outcomes after punctal occlusion with silicone plugs in dry eye syndrome

    Am. J. Ophthalmol.

    (2001)
  • P. Marsh et al.

    Topical nonpreserved methylprednisolone therapy for keratoconjunctivitis sicca in Sjögren syndrome

    Ophthalmology

    (1999)
  • K. Sall et al.

    Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease: CsA Phase 3 Study Group

    Ophthalmology

    (2000)
  • A. Fisher et al.

    (+-)-cis-2-methyl-spiro(1,3-oxathiolane-5,3′) quinuclidine (AF102B): A new M1 agonist attenuates cognitive dysfunctions in AF64A-treated rats

    Neurosci. Lett.

    (1989)
  • M. Segal et al.

    AF102B, a muscarinic M1 receptor agonist, mimics some effects of acetylcholine on neurons of rat hippocampus slices

    Eur. J. Pharmacol.

    (1992)
  • H. Masunaga et al.

    Long-lasting salivation induced by a novel muscarinic receptor agonist SNI-2011 in rats and dogs

    Eur. J. Pharmacol.

    (1997)
  • Y. Iwabuchi et al.

    Sialogogic activities of SNI-2011 compared with those of pilocarpine and McN-A-343 in rat salivary glands: Identification of a potential therapeutic agent for treatment of Sjögren's syndrome

    Gen. Pharmacol.

    (1994)
  • T.G. Beach et al.

    Reduction of cerebrospinal fluid amyloid-beta after systemic administration of M1 muscarinic agonists

    Brain Res.

    (2001)
  • T.E. Daniels et al.

    Association of patterns of labial salivary gland inflammation with keratoconjunctivitis sicca: Analysis of 618 patients with suspected Sjögren's syndrome

    Arthritis Rheum.

    (1994)
  • C. Vitali

    Criteria for the classification of Sjögren's syndrome

    Primer on the Rheumatic Diseases

    (1998)
  • M.E. Stern et al.

    A unified theory of the role of the ocular surface in dry eye

    Adv. Exp. Med. Biol.

    (1998)
  • J.D. Nelson

    Diagnosis of keratoconjunctivitis sicca

    Int. Ophthalmol. Clin.

    (1994)
  • J.D. Nelson et al.

    Cellulose acetate impressions of the ocular surface: Dry eye states

    Arch. Ophthalmol.

    (1983)
  • J.C. Atkinson et al.

    Major salivary gland function in primary Sjögren's syndrome and its relationship to clinical features

    J. Rheumatol.

    (1990)
  • J.P. Craig et al.

    Importance of the lipid layer in human tear film stability and evaporation

    Optom. Vis. Sci.

    (1997)
  • Y. Danjo et al.

    Observation of precorneal tear film in patients with Sjögren's syndrome

    Acta Ophthalmol. Scand.

    (1995)
  • M.A. Lemp

    Tear film: New concepts and implications for the management of the dry eye

    Trans. New Orleans Acad. Ophthalmol.

    (1987)
  • R.I. Fox

    Sjögren's syndrome: Pathogenesis and new approaches to therapy

    Adv. Exp. Med. Biol.

    (1998)
  • S.D. Jaanus

    Ocular side effects of selected systemic drugs

    Optom. Clin.

    (1992)
  • J.C. Atkinson et al.

    Salivary gland dysfunction

    Clin. Geriatr. Med.

    (1992)
  • J.A. Ship et al.

    Diminished submandibular salivary flow in dementia of the Alzheimer type

    J. Gerontol.

    (1990)
  • B.J. Baum

    Salivary gland fluid secretion during aging

    J. Am. Geriatr. Soc.

    (1989)
  • B.J. Baum

    Neurotransmitter control of secretion

    J. Dent. Res.

    (1987)
  • J. Ekstrom

    Autonomic control of salivary secretion

    Proc. Finn. Dent. Soc.

    (1989)
  • D. Zoukhri et al.

    Impaired neurotransmitter release from lacrimal and salivary gland nerves of a murine model of Sjögren's syndrome

    Invest. Ophthalmol. Vis. Sci.

    (2001)
  • C. Eva et al.

    Vasoactive intestinal peptide which coexists with acetylcholine decreases acetylcholine turnover in mouse salivary glands

    J. Pharmacol. Exp. Ther.

    (1985)
  • J. Tornwall et al.

    Distribution of vasoactive intestinal peptide (VIP) and its binding sites in labial salivary glands in Sjögren's syndrome and in normal controls

    Clin. Exp. Rheumatol.

    (1994)
  • R.R. Hodges et al.

    Identification and cellular localization of the components of the VIP signaling pathway in the lacrimal gland

    Adv. Exp. Med. Biol.

    (1998)
  • R. Fox et al.

    Current issues in the diagnosis and treatment of Sjögren's syndrome

    Curr. Opin. Rheumatol.

    (1999)
  • S. Alpert et al.

    Expression of granzyme A in salivary gland biopsies from patients with primary Sjögren's syndrome

    Arthritis Rheum.

    (1994)
  • L. Kong et al.

    Fas and Fas ligand expression in the salivary glands of patients with primary Sjögren's syndrome

    Arthritis Rheum.

    (1997)
  • Y. Andoh et al.

    Morphometric analysis of secretory glands in Sjögren's syndrome

    Am. Rev. Respir. Dis.

    (1993)
  • T.E. Daniels

    Labial salivary gland biopsy in Sjögren's syndrome

    Arthritis Rheum.

    (1984)
  • T.E. Daniels et al.

    Salivary and oral components of Sjögren's syndrome

    Rheum. Dis. Clin. North Am.

    (1992)
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