Dehaye J P, Moran A, Marino A
Laboratoire de Biochimie générale et humaine, Institut de Pharmacie, Université libre de Bruxelles, Belgium.
Arch Oral Biol. 1999 May;44 Suppl 1:S39-43. doi: 10.1016/s0003-9969(99)90014-6.
The response of rat submandibular glands to extracellular purines was tested. In crude cellular suspensions, ATP increased the [Ca2+]i mostly by promoting uptake of extracellular calcium. ATP caused the pHi to drop, a response blocked by chloride channel inhibitors. ATP also inhibited the basal and isoproterenol-stimulated activity of the Na+ -K+ -2Cl-cotransporter. These effects were reproduced by benzoyl-ATP, an agonist of ionotropic purinoceptors. In pure ductal suspensions, ATP activated a metabotropic P2Y1 purinergic receptor coupled to phospholipase C and opened a non-specific cation channel coupled to a P2X7 receptor. Activation of these receptors stimulated a Ca2+ -dependent and a Ca2+ -independent phospholipase A2, the latter resulting in kallikrein secretion. We conclude that purinergic agonists can modulate the activity of both acinar and ductal phases of secretion. Activation of metabotropic receptors coupled to phospholipase C could lead to responses resembling those to muscarinic or adrenergic agonists. Activation of ionotropic receptors could stimulate new intracellular responses also involved in secretory function.
对大鼠下颌下腺对细胞外嘌呤的反应进行了测试。在粗制细胞悬液中，ATP主要通过促进细胞外钙的摄取来增加[Ca2+]i。ATP导致细胞内pH值下降，这种反应被氯离子通道抑制剂阻断。ATP还抑制了Na+-K+-2Cl共转运体的基础活性和异丙肾上腺素刺激的活性。这些效应可被离子型嘌呤受体激动剂苯甲酰ATP重现。在纯导管悬液中，ATP激活了与磷脂酶C偶联的代谢型P2Y1嘌呤能受体，并打开了与P2X7受体偶联的非特异性阳离子通道。这些受体的激活刺激了一种依赖Ca2+的和一种不依赖Ca2+的磷脂酶A2，后者导致激肽释放酶分泌。我们得出结论，嘌呤能激动剂可以调节腺泡和导管分泌阶段的活性。与磷脂酶C偶联的代谢型受体的激活可能导致类似于对毒蕈碱或肾上腺素能激动剂的反应。离子型受体的激活可能刺激也参与分泌功能的新的细胞内反应。
