Nakamoto Tetsuji, Brown David A, Catalán Marcelo A, Gonzalez-Begne Mireya, Romanenko Victor G, Melvin James E
Center for Oral Biology, University of Rochester Medical Center, Rochester, New York 14642, USA.
J Biol Chem. 2009 Feb 20;284(8):4815-22. doi: 10.1074/jbc.M808597200. Epub 2008 Dec 19.
Salivary glands express multiple isoforms of P2X and P2Y nucleotide receptors, but their in vivo physiological roles are unclear. P2 receptor agonists induced salivation in an ex vivo submandibular gland preparation. The nucleotide selectivity sequence of the secretion response was BzATP >> ATP > ADP >> UTP, and removal of external Ca(2+) dramatically suppressed the initial ATP-induced fluid secretion ( approximately 85%). Together, these results suggested that P2X receptors are the major purinergic receptor subfamily involved in the fluid secretion process. Mice with targeted disruption of the P2X(7) gene were used to evaluate the role of the P2X(7) receptor in nucleotide-evoked fluid secretion. P2X(7) receptor protein and BzATP-activated inward cation currents were absent, and importantly, purinergic receptor agonist-stimulated salivation was suppressed by more than 70% in submandibular glands from P2X(7)-null mice. Consistent with these observations, the ATP-induced increases in Ca(2+) were nearly abolished in P2X(7)(-/-) submandibular acinar and duct cells. ATP appeared to also act through the P2X(7) receptor to inhibit muscarinic-induced fluid secretion. These results demonstrate that the ATP-sensitive P2X(7) receptor regulates fluid secretion in the mouse submandibular gland.
唾液腺表达多种P2X和P2Y核苷酸受体亚型，但其在体内的生理作用尚不清楚。P2受体激动剂在离体下颌下腺制备中诱导唾液分泌。分泌反应的核苷酸选择性顺序为BzATP >> ATP > ADP >> UTP，去除细胞外Ca(2+)可显著抑制最初ATP诱导的液体分泌（约85%）。这些结果共同表明，P2X受体是参与液体分泌过程的主要嘌呤能受体亚家族。利用P2X(7)基因靶向破坏的小鼠来评估P2X(7)受体在核苷酸诱发的液体分泌中的作用。P2X(7)受体蛋白和BzATP激活的内向阳离子电流缺失，重要的是，P2X(7)基因敲除小鼠的下颌下腺中，嘌呤能受体激动剂刺激的唾液分泌被抑制了70%以上。与这些观察结果一致，在P2X(7)(-/-)下颌下腺腺泡和导管细胞中，ATP诱导的Ca(2+)增加几乎被消除。ATP似乎也通过P2X(7)受体发挥作用，抑制毒蕈碱诱导的液体分泌。这些结果表明，ATP敏感的P2X(7)受体调节小鼠下颌下腺的液体分泌。
