Berry S A, Gudelsky G A
Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106.
Endocrinology. 1992 Sep;131(3):1207-11. doi: 10.1210/endo.131.3.1354601.
The purpose of the present study was to determine whether neurotensin acts within the arcuate nucleus/median eminence to activate tyrosine hydroxylase (TH) within tuberoinfundibular dopamine neurons. The role of Ca2+/phospholipid-dependent protein kinase (protein kinase-C) in the regulation of TH and its involvement in the neurotensin-induced activation of TH within tuberoinfundibular dopamine (TIDA) neurons also was investigated. The activity of TH within TIDA neurons was assessed by quantification of the formation of 3,4-dihydroxyphenylalanine in the arcuate nucleus/median eminence after inhibition of 3,4-dihydroxyphenylalanine decarboxylase. Neurotensin (0.1-10 nM) increased the activity of TH within the arcuate nucleus/median eminence under in vitro conditions by approximately 80%. The activity of TH in the arcuate nucleus/median eminence also was increased approximately 55% by the phorbol ester 12-O-tetradecanoyl(phorbol-13-acetate) (1-100 nM), which activates protein kinase-C. Sphingosine (10 microM), an inhibitor of protein kinase-C, attenuated the activation of TH within TIDA neurons that was induced by both 12-O-tetradecanoyl(phorbol-13-acetate) and neurotensin. Sphingosine alone did not alter the activity of TH, nor did it alter the (Bu)2cAMP-induced activation of TH in the arcuate nucleus/median eminence. It is concluded that neurotensin acts directly within the arcuate nucleus/median eminence to activate TIDA neurons. Furthermore, it is suggested that the activity of TH within these neurons is enhanced after the activation of protein kinase-C and that protein kinase-C may mediate the neurotensin-induced activation of TH within these hypothalamic dopamine neurons.
本研究的目的是确定神经降压素是否在弓状核/正中隆起内发挥作用，以激活结节漏斗多巴胺能神经元中的酪氨酸羟化酶（TH）。还研究了Ca2+/磷脂依赖性蛋白激酶（蛋白激酶C）在TH调节中的作用及其在神经降压素诱导的结节漏斗多巴胺（TIDA）能神经元中TH激活过程中的参与情况。通过在抑制3,4-二羟基苯丙氨酸脱羧酶后对弓状核/正中隆起中3,4-二羟基苯丙氨酸形成的定量分析，评估TIDA能神经元中TH的活性。在体外条件下，神经降压素（0.1 - 10 nM）使弓状核/正中隆起内TH的活性增加了约80%。佛波酯12-O-十四烷酰佛波醇-13-乙酸酯（1 - 100 nM）可激活蛋白激酶C，它也使弓状核/正中隆起内TH的活性增加了约55%。蛋白激酶C的抑制剂鞘氨醇（10 μM）减弱了由12-O-十四烷酰佛波醇-13-乙酸酯和神经降压素诱导的TIDA能神经元中TH的激活。单独的鞘氨醇既不改变TH的活性，也不改变（Bu）2cAMP诱导的弓状核/正中隆起内TH的激活。结论是神经降压素直接在弓状核/正中隆起内发挥作用以激活TIDA能神经元。此外，提示这些神经元内TH的活性在蛋白激酶C激活后增强，并且蛋白激酶C可能介导神经降压素诱导的这些下丘脑多巴胺能神经元中TH的激活。
