Endogenous ATP potentiates only vasopressin secretion from neurohypophysial terminals
Endogenous ATP potentiates only vasopressin secretion from neurohypophysial terminals
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DOI：
10.1002/jcp.21485
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发表时间：
2008-10-01
影响因子：
5.6
通讯作者：
Lemos, Jose R.
中科院分区：
文献类型：
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作者：
Knott, Thomas K.;Marrero, Hector G.;Lemos, Jose R.
外源性三磷酸腺苷(ATP)诱导内向电流，引起神经垂体终末(NHT)释放精氨酸加压素(AVP)；这两种作用都被P2X2和P2X3拮抗剂苏拉明和PPAIDS所抑制。在这里，我们研究了内源性三磷酸腺苷在神经垂体中的作用。刺激NHT可引起AVP和ATP的释放。ATP可增强AVP的释放，但不能增强催产素(OT)的释放，后者可被苏拉明阻断。在松膜片钳记录中，从完整的神经垂体，苏拉明或PPADS在静态浴中产生动作电位电流的抑制，这可以通过静息膜电位(RMP)的超极化来模仿。相应地，在静态和灌流浴中，NHT的RMP有去极化，而苏拉明或PPADS都能减少这种去极化。我们在静态浴中测量了NHT释放的ATP(3.7+/-0.7微米)的累积。在静态浴中应用苏拉明或PPADS均可降低NHT的猝发刺激电容。最后，在苏拉明或PPAIDS存在的情况下，只有电刺激的完整神经垂体释放的加压素减少。这些数据表明，在刺激过程中，神经垂体释放了足够多的ATP，以使其神经末梢去极化。这将通过打开P2X2和P2X3受体，诱导钙离子内流来实现。随后[Ca~(2+)](I)的升高将进一步增加NHT终末仅刺激释放的加压素。这种嘌呤能反馈机制可能在大多数中枢神经系统突触中具有重要的生理意义。
Exogenous ATP induces inward currents and causes the release of arginine-vasopressin (AVP) from isolated neurohypophysial terminals (NHT); both effects are inhibited by the P2X2 and P2X3 antagonists, suramin and PPAIDS. Here we examined the role of endogenous ATP in the neurohypophysis. Stimulation of NHT caused the release of both AVP and ATP. ATP induced a potentiation in the stimulated release of AVP, but not of oxytocin (OT), which was blocked by the presence of suramin. In loose-patch clamp recordings, from intact neurohypophyses, suramin or PPADS produces an inhibition of action potential currents in a static bath, that can be mimicked by a hyperpolarization of the resting membrane potential (RMP). Correspondingly, in a static versus perfused bath there is a depolarization of the RMP of NHT, which was reduced by either suramin or PPADS. We measured an accumulation of ATP (3.7 +/- 0.7 mu M) released from NHT in a static bath. Applications of either suramin or PPADS to a static bath decreased burst-stimulated capacitance increases in NHT. Finally, only vasopressin release from electrically stimulated intact neurohypophyses was reduced in the presence of Suramin or PPAIDS. These data suggest that there was sufficient accumulation of ATP released from the neurohypophysis during stimulations to depolarize its nerve terminals. This would occur via the opening of P2X2 and P2X3 receptors, inducing an influx of Ca2-. The subsequent elevation in [Ca2+](i) would further increase the stimulated release of only vasopressin from NHT terminals. Such purinergic feedback mechanisms could be physiologically important at most CNS synapses.