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• W2052803537 abstract "One of the common side effects of antihistamine medicines is xerostomia (dry mouth). The current consensus is that antihistamine-induced xerostomia comes from an antimuscarinic effect. Although the effect of antihistamines on salivary secretion is both obvious and significant, the cellular mechanism whereby this happens is still unclear because of the lack of knowledge of histamine signaling in human salivary glands. Here, we have studied histamine receptors and the effect of antihistamines on human submandibular acinar cells. In primary cultured human submandibular gland and a HSG cell line, histamine increased the intracellular Ca²⁺ concentration. The histamine-induced cytosolic free Ca²⁺ concentration ([Ca²⁺]_i) increase was inhibited by histamine H1 receptor-specific antagonists, and the expression of the functional histamine H1 receptor was confirmed by reverse transcription–polymerase chain reaction. Interestingly, histamine pretreatment did not inhibit a subsequent carbachol-induced [Ca²⁺]_i rise without “heterologous desensitization.” Chlorpheniramine inhibited a carbachol-induced [Ca²⁺]_i increase at a 100-fold greater concentration than histamine receptor antagonism, whereas astemizole and cetrizine showed more than 1000-fold difference, which in part explains the xerostomia-inducing potency among the antihistamines. Notably, histamine resulted in translocation of aquaporin-5 to the plasma membrane in human submandibular gland cells and green fluorescent protein-tagged aquaporin-5 expressing HSG cells. We found that histidine decarboxylase and the histamine H1 receptor are broadly distributed in submandibular gland cells, whereas choline acetyltransferase is localized only at the parasympathetic terminals. Our results suggest that human salivary gland cells express histamine H1 receptors and histamine-synthesizing enzymes, revealing the cellular mechanism of antihistamine-induced xerostomia." @default.
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• W2052803537 date "2009-05-14" @default.
• W2052803537 modified "2023-09-23" @default.
• W2052803537 title "Histamine H1 Receptor Induces Cytosolic Calcium Increase and Aquaporin Translocation in Human Salivary Gland Cells" @default.
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• W2052803537 doi "https://doi.org/10.1124/jpet.109.153023" @default.
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