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Age-related Decreases in the Response of Aquaporin-5 to Acetylcholine in Rat Parotid Glands

Department of Pharmacology, Tokushima University School of Dentistry, Kuramoto-cho, Tokushima 770-8504, Japan;

*corresponding author, isikawa{at}dent.tokushima-u.ac.jp

Aquaporin-5 (AQP5) is important in salivary fluid secretion in response to cholinergic and adrenergic stimuli in rat parotid glands. We hypothesized that expression and function of AQP5 might change with age. Acetylcholine and epinephrine induced increases in AQP5 levels in the apical plasma membranes of both young adult and senescent rats. The stimulatory effect of acetylcholine, but not that of epinephrine, on AQP5 levels in the apical plasma membranes of the cells decreased markedly during aging. The quinuclidine derivative, SNI-2011, induced a persistent increase in AQP5 levels in the apical plasma membrane in the cells of both these rats. The amounts of M₃-muscarinic receptor and Gq proteins did not decrease during aging. The age-related alteration in the responsiveness of AQP5 in the cells to these stimuli might account for the concomitant changes in nitric oxide synthase activity. These results suggest that SNI-2011 might have therapeutic benefit for the treatment of age-related xerostomia.

KEY WORDS: aging • parotid gland • aquaporin-5 • acetylcholine • nitric oxide