Crowley W R, Kalra S P
Department of Pharmacology, College of Medicine, University of Tennessee, Memphis 38163.
Synapse. 1988;2(3):276-81. doi: 10.1002/syn.890020316.
Previous studies have suggested that the stimulatory effect of neuropeptide Y (NPY) on the release of luteinizing hormone (LH) in rats may be due to a central action of the peptide that promotes the release of LH-releasing hormone (LHRH) from the hypothalamus, and to an action in the pituitary gland, to potentiate the release of LH induced by LHRH. The objectives of the present experiments were to test 1) whether NPY stimulation of LHRH release requires extracellular Ca++, and 2) whether NPY can exert direct stimulatory effects on the release of LH from anterior pituitary cells. The in vitro release of LHRH from medial basal hypothalamic fragments induced by KCl depolarization (56 mM), but not the basal release, was blocked by omission of Ca++ and addition of 0.1 mM EGTA to the incubation medium and also by cobalt (1 mM). Depolarization-induced release of the peptide was unaffected by nifedipine, diltiazem, or lanthanum. However, the stimulation of LHRH release by NPY (1 microM) still occurred in Ca++ free/EGTA medium. In a second set of experiments, 10 min pulses of NPY (1-100 nM) alone were ineffective in stimulating the release of LH from dispersed, perifused anterior pituitary cells obtained from ovariectomized, untreated or ovariectomized, estrogen-treated rats, under conditions where pulses of LHRH (0.1-10 nM) were consistently effective. A brief increase in LH release was observed during a 30 min exposure to 100 nM NPY in estrogen-pretreated cells, but not from untreated cells, and the effect was not as marked as that produced by LHRH.(ABSTRACT TRUNCATED AT 250 WORDS)
以往的研究表明,神经肽Y(NPY)对大鼠促黄体生成素(LH)释放的刺激作用,可能归因于该肽的中枢作用,即促进下丘脑释放促黄体生成素释放激素(LHRH),以及在垂体中的作用,增强LHRH诱导的LH释放。本实验的目的是测试:1)NPY刺激LHRH释放是否需要细胞外钙离子;2)NPY是否能对垂体前叶细胞释放LH产生直接刺激作用。氯化钾去极化(56 mM)诱导的内侧基底部下丘脑片段中LHRH的体外释放(而非基础释放),在孵育培养基中省略钙离子并添加0.1 mM乙二醇双四乙酸(EGTA)以及添加钴(1 mM)时被阻断。去极化诱导的肽释放不受硝苯地平、地尔硫䓬或镧的影响。然而,在无钙/EGTA培养基中,NPY(1 microM)对LHRH释放的刺激作用仍然存在。在另一组实验中,在LHRH(0.1 - 10 nM)脉冲始终有效的条件下,单独的NPY(1 - 100 nM)10分钟脉冲对来自去卵巢、未处理或去卵巢、雌激素处理大鼠的分散的、经灌流的垂体前叶细胞释放LH没有刺激作用。在雌激素预处理的细胞中,在暴露于100 nM NPY的30分钟内观察到LH释放短暂增加,但未处理的细胞中未观察到,且该作用不如LHRH产生的作用明显。(摘要截短于250字)