组胺能与γ-氨基丁酸能神经传递在间位核神经元信息加工中的作用(英文)

The role of interaction between Histaminergic and GABAergic receptor in gignal process on Cerebellar Interpositus Nucleus Neurons in Vitro

小脑间位核(interpositus nucleus,IN)主要接受γ-氨基丁酸(GABA)能纤维支配,同时接受组胺能纤维的调节.本研究在小脑脑片上研究了GABA和组胺对单个IN神经元电活动的共同作用.持续灌流组胺或同时施加组胺和GABA,81.2%(69/85)神经元,GABA及其激动剂的效应都被组胺削弱(持续灌流n=33;同时施加n=36).这种削弱效应能够被组胺H2受体阻断剂ranitidine(n=10)和PKA抑制剂H-89阻断(n=8),fors-kolin模拟组胺的效应(n=9).结果表明组胺和GABA对IN神经元的电活动具有交互调节作用:通过激活H2受体偶联的G-protein-AC-PKA信号通路,磷酸化GABAB和GABAA受体,降低受体功能.推测受体间的对话的工作模式,可能是整个大脑神经元活动的某些药理作用和生理活动调节的基础;如果对话紊乱,可能导致大脑功能障碍.

Previous studies suggested that the activity of neurons in the cerebellar interpositus nucleus （ IN）, is major under the influence of GABAergic fibers afferent, and also regulation of histaminergic fibers afferent. In this study, the brain slice preparation of adult rats was used to examine the combined effect of y-aminobutyric acid （GABA） and histamine on the spontaneous unitary discharge of IN neurons and the underlying mecha- nism. When the effect of GABA was tested during sequential application of histamine or co-application of GABA and histamine, the magnitude of GABA-induced response was modified in 81.2% （69/85） of the cells （n = 33, 36）. Histamine-induced diminishment of GABA response was abolished by the H2 receptor antagonist ranit- idine （n = 10）, and also prevented by PKA inhibitor H-89 （n = 8）. And histamine-induced diminishment of GABA response was mimicked by the adenylyl cyclase activator （AC） forskolin （n = 9）. Our results indicated that a reciprocal modulation between the effects of GABA and histamine on neuronal firing activity via Hi recep- tors and H2 receptors linked intracellular G-protein-AC-PKA signaling pathway, and result in an activation of in- tracellular phosphmylation of GABAR and GABAA receptors, ultimately, a depression of GABA receptor func- tion, suggesting that the disruption of the working model of receptors cross-talk may be responsible for some ofthe pharmacological action and physiological regulation of neuronal activity through the brain.