Ji Shu-Mei, Wang Ze-Min, Li Xue-Ping, He Rui-Rong
Department of Physiology, Hebei Medical University, Shijazhuang 050017, China.
Sheng Li Xue Bao. 2004 Jun 25;56(3):328-34.
To define the action sites of adrenomedullin (ADM) in the rat brain, and to examine whether neuronal NO may participate in the actions of ADM, the present study was undertaken to examine the effects of i.c.v. administration of ADM on the induction of Fos protein and on nitric oxide-producing neurons in rat brain nuclei involved in cardiovascular regulation, using double immunohistochemical method for Fos and neuronal nitric oxide synthase (nNOS). Following i.c.v. administration of ADM (1 nmol/kg, 3 nmol/kg), Fos-like immunoreactivity neurons were markedly increased in several brain areas of the rat, including the nucleus of the solitary tract (NTS), the area postrema, the locus coeruleus, the parabrachial nucleus and the nucleus paragigantocelluaris laterialis (PGL) in the brainstem, the paraventricular nucleus (PVN), the supraoptic nucleus (SON) and the ventromedial hypothalamic nucleus in the hypothalamus, as well as the central amygdaloid nucleus and the lateral habenular nucleus in the forebrain. Following i.c.v. injection of ADM (1 nmol/kg, 3 nmol/kg), the number of double-labeled neurons for Fos and nNOS was increased in the PVN and SON. Small numbers of double-labeled neurons were also found in the NTS and PGL following i.c.v. injection of ADM (3 nmol/kg), while i.c.v. injection of ADM (1 nmol/kg) did not change the number of double-labeled neurons in the NTS and PGL. Pretreatment with calcitonin gene-related peptide receptor antagonist CGRP(8-37) (30 nmol/kg) significantly reduced the action of ADM (3 nmol/kg) in the brain. These results suggest that centrally administered ADM may increase the expression of c-fos in the forebrain, the hypothalamus and the brainstem and activate nitric oxide-producing neurons in the PVN, SON, NTS and PGL. These effects may be partly mediated by CGRP receptors.
为了确定肾上腺髓质素（ADM）在大鼠脑中的作用位点，并研究神经元型一氧化氮（NO）是否参与ADM的作用，本研究采用Fos和神经元型一氧化氮合酶（nNOS）的双重免疫组织化学方法，探讨脑室内注射ADM对参与心血管调节的大鼠脑核中Fos蛋白诱导及一氧化氮产生神经元的影响。脑室内注射ADM（1 nmol/kg，3 nmol/kg）后，大鼠的几个脑区中Fos样免疫反应性神经元明显增加，包括脑干中的孤束核（NTS）、最后区、蓝斑、臂旁核和外侧巨细胞旁核（PGL），下丘脑的室旁核（PVN）、视上核（SON）和腹内侧下丘脑核，以及前脑的中央杏仁核和外侧缰核。脑室内注射ADM（1 nmol/kg，3 nmol/kg）后，PVN和SON中Fos和nNOS双标记神经元的数量增加。脑室内注射ADM（3 nmol/kg）后，NTS和PGL中也发现少量双标记神经元，而脑室内注射ADM（1 nmol/kg）并未改变NTS和PGL中双标记神经元的数量。用降钙素基因相关肽受体拮抗剂CGRP(8 - 37)（30 nmol/kg）预处理可显著降低ADM（3 nmol/kg）在脑中的作用。这些结果表明，中枢给予ADM可能会增加前脑、下丘脑和脑干中c-fos的表达，并激活PVN、SON、NTS和PGL中的一氧化氮产生神经元。这些作用可能部分由CGRP受体介导。
