Subcellular distribution of aquaporin 5 in salivary glands in primary Sjögren's syndrome

Beroukas, Dimitra; Hiscock, Jenny; Jönsson, Roland; Waterman, Sally A.; Gordon, Tom P.

doi:10.1016/s0140-6736(01)06900-8

Cited by 95 publications

(68 citation statements)

References 3 publications

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“…We suggest that the increased number of M3R in acini are exposed to lower levels of acetylcholine due to blocking autoantibodies and furthermore, even when activated, the subsequent intracellular signaling events are downregulated compared with control. This would be consistent with the unaltered levels of aquaporin-5 in pSS in spite of increased M3R density (Beroukas et al, 2001). …”

Section: Are the Increased Numbers Of M3r Functional?supporting

confidence: 80%

“…These events in turn allow water excretion to occur. We have recently demonstrated that there is no difference in AQP5 expression in pSS versus control acini (Beroukas et al, 2001), suggesting that the M3 receptors are simply not being activated, are not fully functional, or are not coupled efficiently to intracellular signaling mechanisms. Consistent with the latter proposal, Dawson et al (2001) demonstrated using patch clamp electrophysiology and measures of intracellular calcium concentration, a decreased sensitivity of muscarinic receptors in pSS LSG.…”

Section: Are the Increased Numbers Of M3r Functional?mentioning

confidence: 99%

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Up-regulation of M3-Muscarinic Receptors in Labial Salivary Gland Acini in Primary Sjögren's Syndrome

Beroukas

Goodfellow

Hiscock

et al. 2002

Laboratory Investigation

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SUMMARY: M3-muscarinic receptors (M3R) mediate parasympathetic cholinergic neurotransmission to salivary and lacrimal glands, and autoantibodies to these receptors have been implicated in sicca symptoms and autonomic dysfunction in Sjögren's syndrome. We have investigated the expression of M3R in paraffin-embedded labial salivary glands (LSG) from seven patients with primary Sjögren's syndrome (pSS) and five healthy controls using high-resolution confocal microscopy and an affinitypurified goat polyclonal antibody raised against the COOH-terminal sequence of the human M3R. Immunolocalization of M3R was similar in control and pSS glands, with punctate staining of M3R in the basal membrane of acinar cells and in the luminal and abluminal membrane of myoepithelial cells. Bright, granular M3R staining was also detected in the cytoplasm and membranes of all intercalated and striated ducts, and infiltrating lymphocytes in pSS. All immunoreactivity was specifically blocked by the immunizing peptide. An increase in M3R expression specifically in acini in pSS was demonstrated by a 30% increase in receptor number per cluster and a 68% increase in the number of clusters in the membrane. This up-regulation is consistent with inhibition of parasympathetic neurotransmission, possibly by antagonistic autoantibodies to M3R. The up-regulation, rather than down-regulation, of M3R in acini of pSS LSG can explain the effectiveness of muscarinic agonists in treating sicca symptoms in pSS. (Lab Invest 2002, 82:203-210).

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Section: Are the Increased Numbers Of M3r Functional?supporting

confidence: 80%

Section: Are the Increased Numbers Of M3r Functional?mentioning

confidence: 99%

Up-regulation of M3-Muscarinic Receptors in Labial Salivary Gland Acini in Primary Sjögren's Syndrome

Beroukas

Goodfellow

Hiscock

et al. 2002

Laboratory Investigation

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“…In other epithelia, where areanormalized rates of fluid absorption/secretion are much lower, AQPs are not required for transepithelial fluid transport, as found for tear fluid secretion by lacrimal gland , sweat secretion (Song et al, 2002), alveolar fluid absorption (Bai et al, 1999;, and airway fluid absorption . Involvement of AQP-in the reduced tear fluid secretion in Sjogren's syndrome has been suggested (Tsubota et al, 2001), though subsequently refuted (Beroukas et al, 2001). AQPs and lacrimal gland function will not be discussed further based on the negative phenotype from our lab and others Sasaki et al, 2007).…”

Section: Aqp Roles Related To Aqp-facilitated Water Transportmentioning

confidence: 93%

Functions of aquaporins in the eye

Verkman

Ruiz-Ederra

Levin

2008

Progress in Retinal and Eye Research

171

117

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The aquaporins (AQPs) are integral membrane proteins whose main function is to transport water across cell membranes in response to osmotic gradients. At the ocular surface, AQP1 is expressed in corneal endothelium, AQP3 and AQP5 in corneal epithelium, and AQP3 in conjunctival epithelium. AQPs are also expressed in lens fiber cells (AQP0), lens epithelium (AQP1), ciliary epithelium (AQP1, AQP4) and retinal Müller cells (AQP4). Mutations in AQP0 produce congenital cataracts in humans. Analysis of knockout mice lacking individual AQPs suggests their involvement in maintenance of corneal and lens transparency, corneal epithelial repair, intraocular pressure regulation, retinal signal transduction and retinal swelling following injury. The mouse phenotype findings implicate AQPs as potential drug targets for therapy of elevated intraocular pressure and ocular disorders involving the cornea, lens and retina. However, much research remains in defining cell-level mechanisms for the ocular AQP functions, in establishing the relevance to human eye disease of conclusions from knockout mice, and in developing AQPmodulating drugs.

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“…The essential role of AQP5 has been shown in the study of AQP5 gene knockout mice, which demonstrated significantly increased lethality of the embryo and problems related with water homeostasis (8,9). In addition, defective cellular trafficking was noted in the lacrimal gland and salivary gland biopsies from patients with Sjögren's syndrome but not in patients with non-Sjögren's dry eye and dry mouth (10,11), although there are some opposite reports (12).…”

Section: Introductionmentioning

confidence: 99%

Trafficking of GFP-AQP5 chimeric proteins conferred with unphosphorylated amino acids at their PKA-target motif (152SRRTS) in MDCK-II cells

et al. 2009

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Subcellular distribution of aquaporin 5 in salivary glands in primary Sjögren's syndrome

Cited by 95 publications

References 3 publications

Up-regulation of M3-Muscarinic Receptors in Labial Salivary Gland Acini in Primary Sjögren's Syndrome

Up-regulation of M3-Muscarinic Receptors in Labial Salivary Gland Acini in Primary Sjögren's Syndrome

Functions of aquaporins in the eye

Trafficking of GFP-AQP5 chimeric proteins conferred with unphosphorylated amino acids at their PKA-target motif (152SRRTS) in MDCK-II cells

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