Akamatsu N, Inenaga K, Yamashita H
Department of Physiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
J Neuroendocrinol. 1993 Oct;5(5):517-22. doi: 10.1111/j.1365-2826.1993.tb00516.x.
The effects of natriuretic peptides on electrical activity and cellular cGMP levels were studied in neurons of the supraoptic nucleus (SON) of rat hypothalamic slice preparations. Intracellular and extracellular recordings showed that bath application of A type natriuretic peptide (ANP) at 100 nM or B type natriuretic peptide (BNP) at 100 to 300 nM decreased the firing rate and hyperpolarized the membrane potential in phasically firing (putative vasopressin) neurons. Non-phasically firing (putative oxytocin) neurons did not respond to these natriuretic peptides in firing rate or membrane potential. The membrane-permeable cGMP analogue 8-bromo cGMP at 0.5 mM and the phosphodiesterase inhibitor 3/isobutyl-1-methylxanthine (IBMX) at 50 microM mimicked the inhibitory effects of ANP and BNP. The specific inhibitor of cGMP phosphodiesterase 1-(3-chloroanilino)-4-phenylphthalazine+ ++ (MY5445) at 30 microM also decreased the firing rate of SON neurons. The cGMP-dependent protein kinase inhibitor N-(2-(methylamino)ethyl)-5-isoquinoline-sulfonamide dihydrochloride (H8) at 1 microM abolished the inhibition by natriuretic peptides. We measured cGMP and cAMP contents in discrete SON regions and compared the change of contents before and after application of ANP and BNP. The increases in cellular cGMP accumulation were 430% for ANP and 120% for BNP, although they did not cause significant change of cAMP accumulation. The results suggest that the inhibitory effects of natriuretic peptides on putative vasopressin neurons are mediated through cGMP and cGMP-dependent protein kinase.
在大鼠下丘脑切片制备的视上核（SON）神经元中，研究了利钠肽对电活动和细胞环磷酸鸟苷（cGMP）水平的影响。细胞内和细胞外记录显示，在浴槽中加入100 nM的A型利钠肽（ANP）或100至300 nM的B型利钠肽（BNP），可降低相位性放电（假定为血管加压素）神经元的放电频率并使膜电位超极化。非相位性放电（假定为催产素）神经元的放电频率或膜电位对这些利钠肽无反应。0.5 mM的膜通透性cGMP类似物8-溴cGMP和50 μM的磷酸二酯酶抑制剂3-异丁基-1-甲基黄嘌呤（IBMX）模拟了ANP和BNP的抑制作用。30 μM的cGMP磷酸二酯酶特异性抑制剂1-（3-氯苯胺基）-4-苯基酞嗪（MY5445）也降低了SON神经元的放电频率。1 μM的cGMP依赖性蛋白激酶抑制剂N-（2-（甲氨基）乙基）-5-异喹啉磺酰胺二盐酸盐（H8）消除了利钠肽的抑制作用。我们测量了SON离散区域中的cGMP和cAMP含量，并比较了应用ANP和BNP前后含量的变化。尽管ANP和BNP未引起cAMP积累的显著变化，但细胞内cGMP积累的增加分别为430%和120%。结果表明，利钠肽对假定的血管加压素神经元的抑制作用是通过cGMP和cGMP依赖性蛋白激酶介导的。
