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Shivaram Selvam, Austin K. Mircheff, Samuel C. Yiu; Diverse Mediators Modulate the Chloride Ion Fluxes That Drive Lacrimal Fluid Production. Invest. Ophthalmol. Vis. Sci. 2013;54(4):2927-2933. doi: 10.1167/iovs.12-10202.
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To learn whether locally expressed and systemic mediators might modulate the cholinergically induced transepithelial Cl− fluxes that underlie lacrimal fluid production.
Reconstituted epithelial monolayers were exposed to a submaximal dose of the muscarinic agonist, carbachol (CCh), or to one of several paracrine mediators for 18 hours, then acutely stimulated with an optimal dose of CCh. Secretory Cl− fluxes were assessed as negative short-circuit currents (I SC).
Exposure to IL-6 at concentrations of 1 and 10 ng/mL and IL-1β at 10 ng/mL significantly decreased CCh-induced Cl− secretion. Prolactin decreased CCh-induced Cl− secretion, but the extent of the decrease diminished as the prolactin concentration increased from 20 to 200 ng/mL. CCh, 10 μM, prevented CCh, 100 μM, from eliciting Cl− secretion. Exposure to histamine, 10 mM, prevented formation of confluent monolayers. Exposure to histamine, 1 mM, decreased CCh-induced Cl− secretion, whereas exposure to 5-HT, 1 mM, potentiated CCh-induced Cl− secretion.
Chronic exposure to inflammatory cytokines may significantly impair cholinergically induced lacrimal fluid production. Concentrations of prolactin within the high range of normal values also may impair fluid production, but this effect is reversed at levels associated with pregnancy. Autonomic neurotransmitters and paracrine mediators that signal through different G protein–coupled receptors appear to exert varying influences, which range from complete suppression to potentiation of cholinergically induced fluid production. Thus, some hormones and paracrine mediators may impair secretion in apparently homeostatic glands as well as diseased glands, whereas mediators produced by certain immune cell infiltrates may actually enhance fluid formation.
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