Contribution of two ionotropic purinergic receptors to ATP responses in submandibular gland ductal cells

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• 作者：Sté ; phanie Pochet ; Mikel Garcia-Marcos ; Michè ; le Seil ; Anne Otto ; Aida Marino ; Jean-Paul Dehaye
• 关键词：P2X₇ receptors ; KO mice ; Purinergic ; IL-1β ; Saliva ; Exocrine glands
• 刊名：Cellular Signalling
• 出版年：2007
• 出版时间：October 2007
• 年：2007
• 卷：19
• 期：10
• 页码：2155-2164
• 全文大小：532 K

文摘

The effect of extracellular ATP on salivary gland function was compared in wild-type (WT) and P2X₇ knockout (KO) mice. The increase in the intracellular concentration of calcium ([Ca²⁺]_i) in response to carbachol was similar in submandibular ductal cells of WT and KO mice. ATP and its analog, benzoyl-ATP, induced a sustained increase in the [Ca²⁺]_i in WT animals. In KO mice, ATP slightly and transiently increased the [Ca²⁺]_i and benzoyl-ATP had no effect. The response to ATP of WT but not KO mice was blocked by KN-62, Coomassie blue and magnesium. The small response of ATP observed in KO mice was completely blocked in the absence of extracellular calcium, unchanged by U73122 and potentiated by ivermectin indicating the probable involvement of a P2X₄ receptor. A RT-PCR and a Western blot confirmed the presence of these receptors in ducts of both WT and KO mice. ATP increased the permeability of the cells to ethidium bromide and stimulated a phospholipase A₂ activity in WT but not KO mice. Mice submandibular gland cells secreted IL-1β but this secretion was not modified by ATP and was similar in both groups of animals. The volume of saliva provoked by pilocarpine and the concentration of proteins, sodium and chloride in this saliva was similar in both groups of animals. The concentration of potassium was higher in KO mice.

We can conclude that the major purinergic receptors expressed in mice submandibular ductal cells are P2X₇ receptors but that P2X₄ receptors are also involved in some ATP effects.