Kinney G A, Emmerson P J, Miller R J
Department of Pharmacological and Physiological Sciences, The University of Chicago, Chicago Illinois, 60637, USA.
J Neurosci. 1998 May 15;18(10):3489-500. doi: 10.1523/JNEUROSCI.18-10-03489.1998.
It is thought that galanin, a 29 amino acid neuropeptide, is involved in various neuronal functions, including the regulation of food intake and hormone release. Consistent with this idea, galanin receptors have been demonstrated throughout the brain, with high levels being observed in the hypothalamus. However, little is known about the mechanisms by which galanin elicits its actions in the brain. Therefore, we studied the effects of galanin and its analogs on synaptic transmission using an in vitro slice preparation of rat hypothalamus. In arcuate nucleus neurons, application of galanin resulted in an inhibition of evoked glutamatergic EPSCs and a decrease in paired-pulse depression, indicating a presynaptic action. The fragments galanin 1-16 and 1-15 produced a robust depression of synaptic transmission, whereas the fragment 3-29 produced a lesser degree of depression. The chimeric peptides C7, M15, M32, and M40, which have been reported to antagonize some actions of galanin, all produced varying degrees of depression of evoked EPSCs. In a minority of cases, C7, M15, and M40 antagonized the actions of galanin. Analysis of mEPSCs in the presence of TTX and Cd2+, or after application of alpha-latrotoxin, indicated a site of action for galanin downstream of Ca2+ entry. Thus, our data suggest that galanin acts via several subtypes of presynaptic receptors to depress synaptic transmission in the rat arcuate nucleus.
甘丙肽是一种由29个氨基酸组成的神经肽，被认为参与多种神经元功能，包括食物摄入调节和激素释放。与这一观点一致的是，甘丙肽受体已在全脑被证实存在，在下丘脑中观察到其高水平表达。然而，关于甘丙肽在脑中发挥作用的机制却知之甚少。因此，我们使用大鼠下丘脑的体外脑片制备技术，研究了甘丙肽及其类似物对突触传递的影响。在弓状核神经元中，应用甘丙肽导致诱发的谷氨酸能兴奋性突触后电流（EPSCs）受到抑制，成对脉冲抑制降低，表明其具有突触前作用。甘丙肽1 - 16和1 - 15片段对突触传递产生了强烈抑制，而3 - 29片段产生的抑制程度较小。据报道，嵌合肽C7、M15、M32和M40可拮抗甘丙肽的某些作用，但它们均对诱发的EPSCs产生了不同程度的抑制。在少数情况下，C7、M15和M40可拮抗甘丙肽的作用。在存在河豚毒素（TTX）和镉离子（Cd2+）的情况下，或应用α - 银环蛇毒素后，对微小兴奋性突触后电流（mEPSCs）的分析表明，甘丙肽的作用位点在钙离子内流下游。因此，我们的数据表明，甘丙肽通过几种突触前受体亚型发挥作用，从而抑制大鼠弓状核的突触传递。
