Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0314719 (dry eye)
 2,625 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We used the pH-sensitive fluorescent dye 2',7'-bis(2-carboxyethyl)-5(6')-carboxyfluorescein to monitor the recovery of the intracellular pH (pHi) of rat parotid acini from an NH4(+)-induced alkaline load. This recovery was markedly inhibited by the loop diuretic bumetanide and by Cl- removal, indicating that it is largely due to NH4+ entry via the basolateral Na(+)-K(+)-2Cl- cotransporter. The rate of recovery of pHi was enhanced threefold by pretreatment (37.5 s) with isoproterenol (K1/2 = 21.5 nM) or norepinephrine (in the presence of phentolamine), and blocked by the beta 1-specific antagonist atenolol, indicating an upregulation of cotransport activity by beta 1-adrenergic stimulation. The effect of isoproterenol was prevented by protein kinase inhibitors and mimicked by cAMP analogues, and by maneuvers known to increase cytosolic cAMP levels in these cells, consistent with the involvement of protein kinase A. Physiologically, such an upregulation of the acinar Na(+)-K(+)-2Cl- cotransporter would lead to an increase in acinar chloride uptake across the basolateral membrane, and consequently, an increase in overall chloride and fluid secretion. Prevention of this upregulation by beta-blockers and possibly by other commonly used clinical agents may account for the dry mouth and dry eyes experienced by some patients taking these medications.
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PMID:Beta-adrenergic upregulation of the Na(+)-K(+)-2Cl- cotransporter in rat parotid acinar cells. 131 47

A double-masked cross-over comparison of the ocular hypotensive effect in 19 glaucoma patients between timolol 0.5% - a non-selective beta-blocking agent - and metoprolol 3% - a beta 1-selective blocking agent - disclosed a greater pressure lowering effect (mean 9%, median 7% more) with timolol in a treatment period of 1 month. In patients on timolol treatment 47% - 60% of the eyes could be controlled on an IOP level less than 20 mmHg compared to 34% - 47% of the eyes treated with metoprolol. Metoprolol induced a transitory burning sensation in the eyes of 58% patients compared to 26% treated with timolol. Possible signs of dry eyes manifestations as measured by break-up time, rose bengal and fluorescein 1% staining, tear osmolality and Schirmer test I developed in both the timolol (4 patients) and metoprolol (3 patients) treated group. No significant influence on blood pressure and heart rate was observed. In none had the visual field or visual acuity deteriorated at the end of the study.
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PMID:Timolol and metoprolol in glaucoma. A comparison of the ocular hypotensive effect, local and systemic tolerance. 703 54

This study examines the canine model of keratoconjunctivitis sicca (KCS, 'dry eye') in order to establish the biochemical basis of altered ocular mucin secretion in this condition. It follows a previous examination of ocular mucins in the normal dog. Mucus was collected by suction from the ocular surface of dogs with KCS, and dispersed in guanidine hydrochloride containing a cocktail of protease inhibitors. Caesium chloride density gradient centrifugation was used to separate floating 'rafts' of cell membranes from gradients containing secreted mucins. Gradient fractions were collected into pools on the basis of differential staining by Periodic Acid Schiff, Wheat Germ Agglutinin, and antibodies to MUC5AC peptide. High molecular weight glycoproteins were purified from the pooled material by gel filtration chromatography. Membrane-associated glycoproteins were also derived from the membrane rafts using octyl glucoside extraction and/or reduction and alkylation. Secreted mucins and membrane extracts from KCS samples were compared to equivalent material obtained from normal eyes. Density gradient staining profiles for normal and KCS mucus were similar over the buoyant density range typical for secreted mucins, enabling the collection of identical pools of gradient fractions for direct comparison. The following differences were observed in KCS secreted mucins compared to normal samples: an increase in the proportion of mucin with low buoyant density; a decrease in mannose content detected with Concanavalin A lectin; an increase in N-acetylglucosamine structures detected with Lycopersicon esculentum lectin; increased migration and lack of evidence for distinct subunit structure on agarose gels. In membrane extracts, the main difference was the presence of T antigen (Gal beta 1-3GalNAc) in KCS. These results demonstrate alterations in the subunit linkage of mucins in KCS, and suggest that glycosylation, core protein expression and/or post-synthetic modification of ocular surface mucins may also be changed.
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PMID:Biochemical analysis of ocular surface mucin abnormalities in dry eye: the canine model. 999 Mar 35