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Secretory effects of ATP on nontransformed dog pancreatic duct epithelial cells.

机译:ATP对未转化的狗胰管上皮细胞的分泌作用。

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Extracellular triphosphate nucleotides, such as ATP, may regulate various cellular functions through specific cell surface receptors. We examine in this report the different secretory effects of ATP and analogs on nontransformed dog pancreatic duct epithelial cells (PDEC). We observed that 1) ATP, UTP, adenosine 5'-O-(3-thiotriphosphate), and, to a lesser extent, beta, gamma-methylene-ATP, but not adenosine, stimulated 125I- efflux from PDEC, suggesting a primary role for P2Y2 receptors, 2) ATP-stimulated 125I- efflux was inhibited by 5-nitro-2-(3-phenylpropylamino)benzoic acid, diphenylamine-2-carboxylate, and DIDS, suggesting mediation through Ca2+-activated Cl- channels, 3) ATP stimulated an 86Rb+ efflux sensitive to BaCl2 and charybdotoxin, thus likely occurring through Ca2+-activated K+ channels, 4) serosal or luminal addition of UTP activated apical Cl- conductance and basolateral K+ conductance when nystatin-permeabilized PDEC were studied in an Ussing chamber, suggesting the expression of P2Y2 receptors on both sides of the cell, 5) ATP stimulated mucin secretion, and 6) ATP increases intracellular Ca2+ concentration ([Ca2+]i). In conclusion, ATP and UTP interact with P2Y2 receptors on nontransformed PDEC to increase [Ca2+]i, stimulate mucin secretion, and activate ion conductances; these findings have implications for pancreatic exocrine function in both health and disease, such as cystic fibrosis.
机译:细胞外三磷酸核苷酸,例如ATP,可能通过特定的细胞表面受体调节各种细胞功能。我们在这份报告中检查了ATP和类似物对未转化的狗胰管上皮细胞(PDEC)的不同分泌作用。我们观察到1)ATP,UTP,腺苷5'-O-(3-硫代三磷酸),以及在较小程度上,β,γ-亚甲基-ATP而非腺苷刺激了PDEC的125I外排,表明这是主要的P2Y2受体的作用; 2)5-硝基-2-(3-苯基丙基氨基)苯甲酸,二苯胺-2-羧酸盐和DIDS抑制ATP刺激的125I外排,表明通过Ca2 +激活的Cl-通道进行介导,3 )ATP刺激了对BaCl2和Charybdotoxin敏感的86Rb +外排,因此很可能是通过Ca2 +激活的K +通道发生的; 4)在Ussinging Room中研究了制霉菌素透化的PDEC时,浆膜或腔内添加了UTP激活的根尖Cl-电导和基底外侧K +电导。 ,提示细胞两侧P2Y2受体的表达,5)ATP刺激的粘蛋白分泌和6)ATP增加了细胞内Ca2 +浓度([Ca2 +] i)。总之,ATP和UTP与非转化PDEC上的P2Y2受体相互作用,从而增加[Ca2 +] i,刺激粘蛋白分泌并激活离子电导。这些发现对胰腺外分泌功能在健康和疾病(如囊性纤维化)中都有影响。

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