Mönnikes H, Lauer G, Arnold R
Department of Internal Medicine, Philipps-University of Marburg, Germany.
Brain Res. 1997 Oct 3;770(1-2):277-88. doi: 10.1016/s0006-8993(97)00865-2.
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 micrograms/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 micrograms 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 of 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.
腹腔注射硫酸化胆囊收缩素八肽（CCK-8S）已被证明可诱导孤束核（NTS）、最后区（AP）、迷走神经背核复合体（DVC）的感觉部分以及下丘脑室旁核（PVN）的神经元活动发生变化，这是通过c-fos表达的激活来确定的。通过c-Fos免疫组织化学方法，研究了在清醒大鼠腹腔注射CCK-8S时外周CCK是否影响蓝斑（LC）/蓝斑下核（SC）的神经元活动。腹腔注射CCK-8S（分别为25、50和100微克/千克）剂量依赖性地使LC/SC中c-Fos-LI阳性细胞/切片的平均数量分别增加了5.9倍、8.2倍和11.7倍。用CCK-A受体拮抗剂MK-329（地伐西匹；腹腔注射1毫克/千克和2毫克/千克）预处理分别使CCK诱导的LC/SC中c-fos表达增加减少了54%和75%；CCK-B受体拮抗剂L-365,260没有效果。迷走神经周围辣椒素预处理使CCK诱导的LC/SC中c-Fos-LI阳性细胞数量增加减少了65%。相比之下，CCK-A拮抗剂地伐西匹（腹腔注射1毫克/千克和2毫克/千克）使PVN中c-fos表达增加分别减少了76%和88%，NTS中减少了69%和88%，AP中分别减少了86%和83%。辣椒素使PVN中CCK诱导的c-Fos-LI阳性细胞增加减少了64%，NTS中减少了60%，但在AP中仅减少了25%。针对核抗原c-Fos和细胞质抗原酪氨酸羟化酶（TH）的免疫染色显示，在25微克CCK/千克时，LC/SC中所有c-Fos-LI阳性细胞的40%为TH-LI阳性。数据表明，腹腔注射CCK-8S主要通过CCK-A受体的外周作用和辣椒素敏感的迷走神经传入纤维诱导LC/SC、DVC和PVN中神经元活动的调节。这些发现表明，LC/SC参与了外周CCK的中枢神经系统介导的调节作用。
