Rogers Richard C, Hermann Gerlinda E
Laboratory of Autonomic Neurosciences, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
Peptides. 2008 Oct;29(10):1716-25. doi: 10.1016/j.peptides.2008.06.023. Epub 2008 Jul 4.
Cholecystokinin [CCK] is a peptide released as a hormone by the proximal gut in response to the presence of peptones and fatty acid in the gut. Considerable evidence suggests that CCK inhibits feeding behavior and gastric function by acting as a paracrine modulator of vagal afferents in the periphery, especially in the duodenum. CCK is also widely distributed throughout the mammalian brain and appears to function as a neurotransmitter and neuromodulator. More recent studies have suggested that CCK may act directly within the CNS to activate central vagal afferent terminal inputs to the solitary nucleus. We have developed an in vitro calcium imaging method that reveals, for the first time, the direct effects of this peptide on vagal terminals in the solitary nucleus. In vitro imaging reveals that CCK provokes increases in intracellular calcium in vagal afferent terminals as a consequence of a complex interaction between protein kinase A [PKA] and phospholipase C [PLC] transduction mechanisms that open L-type calcium channels and causes endoplasmic reticular [ER] calcium release. The subsequent activation of PKC may be responsible for initiating calcium spiking which is dependent on a TTX-sensitive mechanism. Thus, imaging of the isolated but spatially intact hindbrain slice has allowed a more complete appreciation of the interdependent transduction mechanisms used by CCK to excite identified central vagal afferent fibers and varicosities.
胆囊收缩素[CCK]是近端肠道在肠道中存在胨和脂肪酸时作为一种激素释放的肽。大量证据表明，CCK通过作为外周尤其是十二指肠中迷走神经传入纤维的旁分泌调节剂来抑制摄食行为和胃功能。CCK也广泛分布于整个哺乳动物大脑中，并且似乎作为一种神经递质和神经调节剂发挥作用。最近的研究表明，CCK可能在中枢神经系统内直接起作用，以激活孤束核的中枢迷走神经传入终末输入。我们开发了一种体外钙成像方法，首次揭示了这种肽对孤束核中迷走神经终末的直接作用。体外成像显示，由于蛋白激酶A[PKA]和磷脂酶C[PLC]转导机制之间的复杂相互作用，CCK会引起迷走神经传入终末细胞内钙增加，这种相互作用会打开L型钙通道并导致内质网[ER]钙释放。PKC的后续激活可能负责启动依赖于TTX敏感机制的钙尖峰。因此，对分离但空间完整的后脑切片进行成像，能够更全面地了解CCK用于激发已识别的中枢迷走神经传入纤维和曲张体的相互依赖的转导机制。
