Peripheral administration of cholecystokinin activates c-fos expression in the locus coeruleus/subcoeruleus nucleus, dorsal vagal complex and paraventricular nucleus via capsaicin-sensitive vagal afferents and CCK-A receptors in the rat
Peripheral administration of cholecystokinin activates c-fos expression in the locus coeruleus/subcoeruleus nucleus, dorsal vagal complex and paraventricular nucleus via capsaicin-sensitive vagal afferents and CCK-A receptors in the rat
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DOI：
10.1016/s0006-8993(97)00865-2
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发表时间：
1997-10-03
期刊：
影响因子：
2.9
通讯作者：
Arnold, R
中科院分区：
文献类型：
--
作者：
Monnikes, H;Lauer, G;Arnold, R
腹膜内（i. p.）硫酸化CCK八肽（CCK-8 S）的给药已显示诱导孤束核（NTS）和最后区（AP）、迷走神经背侧复合体（DVC）的感觉部分以及下丘脑室旁核（PVN）中神经元活性的变化，如通过c-fos表达的激活所确定的。在清醒大鼠腹腔内（i. p.）注射CCK-8 S，通过c-Fos免疫组织化学。腹腔注射CCK-8 S（分别为25、50和100 μ g/kg）可剂量依赖性地增加LC/SC中c-Fos-LI阳性细胞/切片的平均数量，分别增加5.9、8.2和11.7倍。用CCK-A受体拮抗剂MK-329（devazepide; lmg/kg和2 mg/kg i. p.）CCK-B受体拮抗剂L-365，260对LC/SC中c-fos表达的增加无明显影响。迷走神经周围辣椒素预处理减少CCK诱导的LC/SC中c-Fos-LI阳性细胞数量增加65%。相比之下，CCK-A拮抗剂devazepide（lmg/kg和2 mg/kg i. p.）在PVN、NTS和AP中，分别降低了76%和88%、69%和88%的c-fos表达增加。辣椒素减少CCK诱导的PVN中c-Fos-LI阳性细胞增加64%，NTS中减少60%，但AP中仅减少25%。对核抗原c-Fos和胞质抗原酪氨酸羟化酶（TH）的免疫染色显示，在25 μ g CCK/kg时，LC/SC中40%的所有c-Fos-LI阳性细胞为TH-LI阳性。这些数据表明，CCK-8 S腹腔注射主要通过对CCK-A受体和辣椒素敏感的迷走神经传入的外周作用来诱导LC/SC、DVC和PVN中的神经元活动的调制。这些结果表明，LC/SC参与CNS介导的外周CCK的调节影响。(C)1997年Elsevier Science B.V.
Intraperitoneal (i.p.) administration of sulfated CCK octapeptide (CCK-8S) has been shown to induce changes in neuronal activity in the nucleus of the solitary tract (NTS) and area postrema (AP), sensory parts of the dorsal vagal complex (DVC), and in the paraventricular nucleus of the hypothalamus (PVN), as determined by activation of c-fos expression. Whether peripheral CCK influences neuronal activity in the locus coeruleus (LC)/subcoeruleus nucleus (SC) was investigated in awake rats at intraperitoneal (i.p.) injection of CCK-8S by c-Fos immunohistochemistry. CCK-8S i.p. (25, 50, and 100 mu g/kg, respectively) dose-dependently increased the average number of c-Fos-LI-positive cells/section in the LC/SC by the factor 5.9, 8.2, and 11.7, respectively. Pretreatment with the CCK-A receptor antagonist MK-329 (devazepide; 1 mg/kg and 2 mg/kg i.p.) reduced the CCK-induced increase in c-fos expression in the LC/SC by 54% and 75%, respectively; the CCK-B receptor antagonist L-365,260 had no effect. Perivagal capsaicin pretreatment diminished the CCK-induced increase in the number of c-Fos-LI-positive cells in the LC/SC by 65%. In comparison, the CCK-A antagonist devazepide (1 mg/kg and 2 mg/kg i.p.) reduced the increase in c-fos expression by 76% and 88% in the PVN, 69% and 88% in the NTS, 86% and 83%, respectively, in the AP. Capsaicin diminished the CCK-induced increase in c-Fos-LI-positive cells in the PVN by 64%, in the NTS by 60%, but in the AP only by 25%. Immunostaining against the nuclear antigen c-Fos and the cytoplasmatic antigen tyrosine hydroxylase (TH) showed that 40% of all c-Fos-LI-positive cells in the LC/SC were TH-LI positive at 25 mu g CCK/kg. The data indicate that CCK-8S i.p. induces modulation of neuronal activity in the LC/SC, DVC and PVN predominantly by peripheral action on CCK-A receptors and capsaicin-sensitive vagal afferents. These findings suggest that the LC/SC is involved in CNS-mediated regulatory influences of peripheral CCK. (C) 1997 Elsevier Science B.V.