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To investigate the role of Cftr in ductal modification of saliva, we determined the ion composition of pilocarpine-stimulated SMG saliva (Fig. 3C). The [Cl?] and [Na+] were significantly increased, whereas the [K+] was not affected, in the Cftr��F/��F mouse CF model. We previously found that in vivo saliva production in response to systemic administration of pilocarpine may not faithfully reflect perturbations of the saliva production machinery (Romanenko et al. 2007). Consequently, we also used an ex vivo, perfused SMG preparation to eliminate the circulating factors and neural inputs that complicate the interpretation of in vivo experiments. A combination of muscarinic (0.3 ��m CCh) and ��-adrenergic (5 ��m IPR) stimulation was used to enhance ductal function (Romanenko http://www.selleckchem.com/products/SRT1720.html et al. 2008). Supplemental Table 1 shows that Na+ and Cl? reabsorption was strongly stimulated in the SMG upon ��-adrenergic stimulation, while K+ secretion was not significantly different, mimicking the in vivo effects of pilocarpine on salivary gland function (compare to Fig. 3C). The salivary flow rates and secretion kinetics were essentially identical in SMG from wild-type and Cftr��F/��F mice (Fig. 4A). In contrast, both the [Cl?] and [Na+] were significantly increased more than 2-fold in Cftr��F/��F saliva, whereas the [K+] was unchanged (Fig. 4B). It should be noted that the [Cl?] in saliva is less than the sum of the [K+] and [Na+], suggesting that other anions must be secreted to maintain electroneutrality. http://en.wikipedia.org/wiki/MERTK http://www.selleckchem.com/products/Adrucil(Fluorouracil).html HCO3?, which permeates the Cftr anion channel and is a major regulator of saliva pH, is the second most abundant physiological anion after Cl? in biological fluids, including saliva (Sommer et al. 1975). Consequently, we measured the saliva pH in littermate wild-type (pH 8.18 �� 0.04, n= 13) and Cftr��F/��F (pH 7.63 �� 0.06, n= 8; P