Kim JH, Park SH, Moon YW, Hwang S, Kim D, Jo SH, Oh SB, Kim JS, Jahng JW, Lee JH, Lee SJ, Choi SY, Park K
Histamine H1 Receptor Induces Cytosolic Calcium Increase And Aquaporin Translocation In Human Salivary Gland Cells. [JOURNAL ARTICLE]
J Pharmacol Exp Ther 2009 May 14.
One of the common side effects of anti-histamine medicines is xerostomia (dry mouth). While the effect of anti-histamines on salivary secretion is both obvious and significant, the cellular mechanism is still unclear due to a lack of knowledge of histamine signaling in human salivary glands. Here we have studied histamine receptors and the effect of anti-histamines on human submandibular acinar cells. In primary cultured human submandibular gland and a HSG cell line, histamine increased the intracellular Ca(2+) concentration. The histamine-induced [Ca(2+)]i increase was inhibited by histamine H1 receptor-specific antagonists, and the expression of the functional histamine H1 receptor was confirmed by RT-PCR. Interestingly, histamine pretreatment did not inhibit a subsequential carbachol-induced [Ca(2+)]i rise without 'heterologous desensitization'. Chlorpheniramine inhibited a carbachol-induced [Ca(2+)]i increase at a 100-fold greater concentration than histamine receptor antagonism, whereas astemizole and cetrizine showed more than 1000-fold difference, which explains in part the xerostomia-inducing potency among the anti-histamines. Notably, histamine resulted in translocation of aquaporin-5 to the plasma membrane in human submandibular gland cells and green fluorescent protein (GFP)-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 anti-histamine-induced xerostomia.
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