Saleh T M, Kombian S B, Zidichouski J A, Pittman Q J
Neuroscience Research Group, University of Calgary, Alberta, Canada.
Neuroscience. 1997 Mar;77(1):23-35. doi: 10.1016/s0306-4522(96)00463-0.
Cholecystokinin and neurotensin are present in fibres innervating the parabrachial nucleus and have previously been shown to modulate the flow of visceral afferent information through the parabrachial nucleus to the cortex in the rat. This study examined the effects of cholecystokinin and neurotensin on synaptic transmission in the parabrachial nucleus using a pontine slice preparation and the nystatin perforated-patch recording technique. Stimulation of the ventral, external lateral portion of the parabrachial nucleus elicited glutamate-mediated, excitatory postsynaptic currents in cells recorded in the parabrachial nucleus. Bath application of neurotensin dose-dependently and reversibly enhanced, while cholecystokinin attenuated, the evoked excitatory postsynaptic current. In addition, the frequency of spontaneous, miniature excitatory postsynaptic currents recorded in parabrachial nucleus cells was significantly increased by neurotensin and decreased by cholecystokinin application. Paired-pulse depression was also enhanced and decreased by neurotensin and cholecystokinin, respectively. These synaptic changes induced by neurotensin and cholecystokinin were not accompanied by changes in input resistance of parabrachial nucleus cells over a wide voltage range (although neurotensin reduced an outwardly rectifying conductance at potentials positive to -20 mV), nor did these peptides alter the inward current induced by a brief bath application of the glutamate agonist, alpha-amino-3-hydroxy-methylisoxazole-4-propionate. The neurotensin antagonist, SR48692 (100 microM), completely and reversibly blocked the neurotensin-induced enhancement of the excitatory postsynaptic current. The non-selective cholecystokinin receptor antagonist, proglumide (100 microM), completely and reversibly blocked the cholecystokinin-induced attenuation of the excitatory postsynaptic current. In addition, the selective cholecystokinin-A receptor antagonist, L-364,718 (10 microM), but not the selective cholecystokinin-B receptor antagonist, L-365,260 (100 microM), blocked the effect of cholecystokinin on synaptic transmission. These results suggest that neurotensin and cholecystokinin act at presynaptic neurotensin and cholecystokinin-A receptors, respectively, to modulate excitatory synaptic transmission in the parabrachial nucleus.
胆囊收缩素和神经降压素存在于支配臂旁核的纤维中，先前的研究已表明，它们可调节大鼠体内通过臂旁核传至皮质的内脏传入信息的流量。本研究采用脑桥切片标本和制霉菌素穿孔膜片钳记录技术，研究了胆囊收缩素和神经降压素对臂旁核突触传递的影响。刺激臂旁核腹外侧外部可在臂旁核记录到的细胞中诱发谷氨酸介导的兴奋性突触后电流。浴加神经降压素剂量依赖性且可逆地增强了诱发的兴奋性突触后电流，而胆囊收缩素则使其减弱。此外，应用神经降压素可使臂旁核细胞中记录到的自发性微小兴奋性突触后电流频率显著增加，应用胆囊收缩素则使其降低。成对脉冲抑制也分别被神经降压素增强和被胆囊收缩素减弱。神经降压素和胆囊收缩素诱导的这些突触变化在很宽的电压范围内并未伴随臂旁核细胞输入电阻的改变（尽管神经降压素在电位正于 -20 mV 时降低了外向整流电导），这些肽也未改变短暂浴加谷氨酸激动剂α-氨基-3-羟基-5-甲基异恶唑-4-丙酸所诱发的内向电流。神经降压素拮抗剂 SR48692（100 μM）完全且可逆地阻断了神经降压素诱导的兴奋性突触后电流增强。非选择性胆囊收缩素受体拮抗剂丙谷胺（100 μM）完全且可逆地阻断了胆囊收缩素诱导的兴奋性突触后电流减弱。此外，选择性胆囊收缩素-A 受体拮抗剂 L-364,718（10 μM）可阻断胆囊收缩素对突触传递的作用，而选择性胆囊收缩素-B 受体拮抗剂 L-365,260（100 μM）则无此作用。这些结果表明，神经降压素和胆囊收缩素分别作用于突触前神经降压素和胆囊收缩素-A 受体，以调节臂旁核的兴奋性突触传递。
