Kadekaro M
Division of Neurosurgery, The University of Texas Medical Branch at Galveston, Galveston, TX 77555-0517, USA.
Braz J Med Biol Res. 2004 Apr;37(4):441-50. doi: 10.1590/s0100-879x2004000400001. Epub 2004 Mar 23.
Nitric oxide (NO), a free radical gas produced endogenously from the amino acid L-arginine by NO synthase (NOS), has important functions in modulating vasopressin and oxytocin secretion from the hypothalamo-neurohypophyseal system. NO production is stimulated during increased functional activity of magnocellular neurons, in parallel with plastic changes of the supraoptic nucleus (SON) and paraventricular nucleus. Electrophysiological data recorded from the SON of hypothalamic slices indicate that NO inhibits firing of phasic and non-phasic neurons, while L-NAME, an NOS inhibitor, increases their activity. Results from measurement of neurohypophyseal hormones are more variable. Overall, however, it appears that NO, tonically produced in the forebrain, inhibits vasopressin and oxytocin secretion during normovolemic, isosmotic conditions. During osmotic stimulation, dehydration, hypovolemia and hemorrhage, as well as high plasma levels of angiotensin II, NO inhibition of vasopressin neurons is removed, while that of oxytocin neurons is enhanced. This produces a preferential release of vasopressin over oxytocin important for correction of fluid imbalance. During late pregnancy and throughout lactation, fluid homeostasis is altered and expression of NOS in the SON is down- and up-regulated, respectively, in parallel with plastic changes of the magnocellular system. NO inhibition of magnocellular neurons involves GABA and prostaglandin synthesis and the signal-transduction mechanism is independent of the cGMP-pathway. Plasma hormone levels are unaffected by i.c.v. 1H-[1, 2, 4]oxadiazolo-[4,3-a]quinoxalin-1-one (a soluble guanylyl cyclase inhibitor) or 8-Br-cGMP administered to conscious rats. Moreover, cGMP does not increase in homogenates of the neural lobe and in microdialysates of the SON when NO synthesis is enhanced during osmotic stimulation. Among alternative signal-transduction pathways, nitrosylation of target proteins affecting activity of ion channels is considered.
一氧化氮（NO）是一种由一氧化氮合酶（NOS）从氨基酸L-精氨酸内源性产生的自由基气体，在调节下丘脑-神经垂体系统中血管加压素和催产素的分泌方面具有重要作用。在大细胞神经元功能活动增强期间，NO的产生会受到刺激，同时视上核（SON）和室旁核会发生可塑性变化。从下丘脑切片的SON记录的电生理数据表明，NO会抑制相位性和非相位性神经元的放电，而NOS抑制剂L-NAME会增加它们的活性。神经垂体激素的测量结果变化更大。然而，总体而言，似乎在前脑持续产生的NO在正常血容量、等渗条件下会抑制血管加压素和催产素的分泌。在渗透刺激、脱水、血容量不足和出血以及血浆中血管紧张素II水平升高时，NO对血管加压素神经元的抑制作用会被解除，而对催产素神经元的抑制作用会增强。这会导致血管加压素比催产素优先释放，这对于纠正液体失衡很重要。在妊娠后期和整个哺乳期，液体稳态会发生改变，SON中NOS的表达分别下调和上调，同时大细胞系统也会发生可塑性变化。NO对大细胞神经元的抑制作用涉及γ-氨基丁酸（GABA）和前列腺素的合成，并且信号转导机制独立于环磷酸鸟苷（cGMP）途径。向清醒大鼠脑室内注射1H-[1,2,4]恶二唑并-[4,3-a]喹喔啉-1-酮（一种可溶性鸟苷酸环化酶抑制剂）或8-溴-cGMP不会影响血浆激素水平。此外，当在渗透刺激期间增强NO合成时，神经叶匀浆和SON的微透析液中的cGMP不会增加。在替代信号转导途径中，考虑了影响离子通道活性的靶蛋白的亚硝基化作用。
