Tsuda K, Yokoo H, Goldstein M
Neurochemistry Research Laboratories, New York University Medical Center, New York 10016.
Hypertension. 1989 Jul;14(1):81-6. doi: 10.1161/01.hyp.14.1.81.
Noradrenergic neurons in the locus ceruleus contain neuropeptide Y and galanin, which project to the hypothalamic region. We have investigated the regulatory mechanisms of these peptides on norepinephrine release in rat hypothalamic slices in vitro. Neuropeptide Y and galanin significantly inhibited the stimulation-evoked [3H]norepinephrine release in a dose-dependent manner (1 Hz: S2/S1 ratio (mean +/- SEM), control 0.947 +/- 0.040, n = 11, neuropeptide Y 1 x 10(-8) M 0.509 +/- 0.013, n = 8, p less than 0.01, neuropeptide Y 1 x 10(-7) M 0.283 +/- 0.021, n = 8, p less than 0.01; galanin 1 x 10(-7) M 0.448 +/- 0.026, n = 8, p less than 0.01, galanin 1 x 10(-6) M 0.261 +/- 0.023, n = 8, p less than 0.01). The inhibition of norepinephrine release by the alpha-2 agonist UK 14,304 was potentiated by neuropeptide Y and galanin. The blockade of the alpha 2-adrenergic receptors by RX 781094 diminished the inhibitory effects of neuropeptide Y and galanin on norepinephrine release. Pretreatment of hypothalamic slices with islet activating protein (a toxin that interferes with the coupling of inhibitory receptors to adenylate cyclase) attenuated the suppression of norepinephrine release by UK 14,304, neuropeptide Y, and galanin. These results support the idea that neuropeptide Y and galanin are involved in the regulation of central adrenergic transmission partially mediated by alpha 2-adrenergic receptors and islet-activating protein-sensitive guanosine triphosphate-binding proteins in rat hypothalamus.
蓝斑中的去甲肾上腺素能神经元含有神经肽Y和甘丙肽，它们投射至下丘脑区域。我们已经在体外研究了这些肽对大鼠下丘脑切片中去甲肾上腺素释放的调节机制。神经肽Y和甘丙肽以剂量依赖的方式显著抑制刺激诱发的[3H]去甲肾上腺素释放（1赫兹：S2/S1比值（平均值±标准误），对照组0.947±0.040，n = 11，神经肽Y 1×10−8 M 0.509±0.013，n = 8，p<0.01，神经肽Y 1×10−7 M 0.283±0.021，n = 8，p<0.01；甘丙肽1×10−7 M 0.448±0.026，n = 8，p<0.01，甘丙肽1×10−6 M 0.261±0.023，n = 8，p<0.01）。α-2激动剂UK 14,304对去甲肾上腺素释放的抑制作用被神经肽Y和甘丙肽增强。RX 781094对α2-肾上腺素能受体的阻断减弱了神经肽Y和甘丙肽对去甲肾上腺素释放的抑制作用。用胰岛激活蛋白（一种干扰抑制性受体与腺苷酸环化酶偶联的毒素）预处理下丘脑切片减弱了UK 14,304、神经肽Y和甘丙肽对去甲肾上腺素释放的抑制作用。这些结果支持这样一种观点，即神经肽Y和甘丙肽参与了大鼠下丘脑部分由α2-肾上腺素能受体和胰岛激活蛋白敏感的鸟苷三磷酸结合蛋白介导的中枢肾上腺素能传递的调节。
