Department of Physiology, University of Otago, Dunedin 9054, New Zealand.
J Physiol. 2009 Dec 1;587(Pt 23):5679-89. doi: 10.1113/jphysiol.2009.180232. Epub 2009 Oct 12.
Dehydration increases vasopressin (antidiuretic hormone) secretion from the posterior pituitary gland to reduce water loss in the urine. Vasopressin secretion is determined by action potential firing in vasopressin neurones, which can exhibit continuous, phasic (alternating periods of activity and silence), or irregular activity. Autocrine kappa-opioid inhibition contributes to the generation of activity patterning of vasopressin neurones under basal conditions and so we used in vivo extracellular single unit recording to test the hypothesis that changes in autocrine kappa-opioid inhibition drive changes in activity patterning of vasopressin neurones during dehydration. Dehydration increased the firing rate of rat vasopressin neurones displaying continuous activity (from 7.1 +/- 0.5 to 9.0 +/- 0.6 spikes s(1)) and phasic activity (from 4.2 +/- 0.7 to 7.8 +/- 0.9 spikes s(1)), but not those displaying irregular activity. The dehydration-induced increase in phasic activity was via an increase in intraburst firing rate. The selective -opioid receptor antagonist nor-binaltorphimine increased the firing rate of phasic neurones in non-dehydrated rats (from 3.4 +/- 0.8 to 5.3 +/- 0.6 spikes s(1)) and dehydrated rats (from 6.4 +/- 0.5 to 9.1 +/- 1.2 spikes s(1)), indicating that kappa-opioid feedback inhibition of phasic bursts is maintained during dehydration. In a separate series of experiments, prodynorphin mRNA expression was increased in vasopressin neurones of hyperosmotic rats, compared to hypo-osmotic rats. Hence, it appears that dynorphin expression in vasopressin neurones undergoes dynamic changes in proportion to the required secretion of vasopressin so that, even under stimulated conditions, autocrine feedback inhibition of vasopressin neurones prevents over-excitation.
脱水会增加后叶垂体分泌血管加压素(抗利尿激素),以减少尿液中的水分流失。血管加压素的分泌由血管加压素神经元的动作电位放电决定,其可以表现为连续的、阶段性(活动和静止交替的时期)或不规则的活动。自分泌 κ 阿片样物质抑制有助于在基础条件下产生血管加压素神经元的活动模式,因此我们使用体内细胞外单位记录来测试以下假设:自分泌 κ 阿片样物质抑制的变化会驱动脱水期间血管加压素神经元活动模式的变化。脱水增加了表现出连续活动(从 7.1±0.5 到 9.0±0.6 个 spikes s-1)和阶段性活动(从 4.2±0.7 到 7.8±0.9 个 spikes s-1)的大鼠血管加压素神经元的放电率,但不增加表现出不规则活动的神经元的放电率。脱水引起的阶段性活动增加是通过爆发内放电率的增加引起的。选择性 μ 阿片受体拮抗剂 nor-binaltorphimine 增加了非脱水大鼠(从 3.4±0.8 到 5.3±0.6 个 spikes s-1)和脱水大鼠(从 6.4±0.5 到 9.1±1.2 个 spikes s-1)中阶段性神经元的放电率,表明在脱水期间,κ 阿片样物质反馈抑制阶段性爆发得到维持。在另一组实验中,与低渗大鼠相比,高渗大鼠的血管加压素神经元中 prodynorphin mRNA 的表达增加。因此,似乎血管加压素神经元中的 dynorphin 表达会根据血管加压素的分泌需求而发生动态变化,即使在刺激条件下,血管加压素神经元的自分泌反馈抑制也可防止过度兴奋。