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半胱氨酸-3对下丘脑可细胞化学检测的葡萄糖-6-磷酸脱氢酶刺激物质浓度的影响。

Effect of hemicholinium-3 on the hypothalamic concentration of a cytochemically detectable glucose-6-phosphate dehydrogenase-stimulating substance.

作者信息

Vargas H M, Brezenoff H E, Morris H R, Panico M, Etienne A, Challand G S, Holland S M, Alaghband Zadeh J, de Wardener H E

机构信息

Biological Research Department, Hoechst-Roussel Pharmaceutical, Somerville, New Jersey.

出版信息

J Cardiovasc Pharmacol. 1994 Nov;24(5):773-8. doi: 10.1097/00005344-199424050-00012.

Abstract

Hypothalamus and plasma of salt-loaded rats, spontaneously hypertensive rats (SHR), and hypertensive reduced renal mass rats (RRM), and the plasma of patients with essential hypertension and of Milan hypertensive rats contain an increased concentration of a cytochemically detectable glucose-6-phosphate dehydrogenase (G6PD)-stimulating substance that has properties similar to that of a possible choline derivative di-methyl methylene immonium ion. Intracerebroventricular (i.c.v.) administration of hemicholinium-3 (HC-3) selectively blocks high-affinity neuronal choline uptake, inhibits brain acetylcholine (ACh) synthesis, and decreases arterial pressure in SHR through an inhibiting effect on hypothalamic cholinergic function. The experiments were performed to study the effect of centrally administered HC-3 on the content of the cytochemically detectable cholinelike substance in hypothalamus and plasma of SHR. HC-3 or saline was infused into the lateral cerebral ventricle for 6 days with a minipump in 14 SHR. On day 7, the hypothalamic and plasma concentration of the cytochemically detectable substance was significantly reduced in rats that received HC-3. The hypothalamic concentration was 225 +/- 95.6 x 10(8) G6PD U per hypothalamus (range 38.2-775) in SHR that received saline and 1.037 +/- 0.45 x 10(8) G6PD U (range 0.112-3.61) (p < 0.05) in SHR that received HC-3. The respective plasma concentrations were 284.9 +/- 26 U/ml (range 192-374) and 72.7 +/- 14.7 U/ml (range 24-119) (p < 0.05). The findings are consistent with the physicochemical evidence, which suggests that the cytochemically detectable substance is a choline derivative.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

盐负荷大鼠、自发性高血压大鼠(SHR)、肾质量减少的高血压大鼠(RRM)的下丘脑和血浆,以及原发性高血压患者和米兰高血压大鼠的血浆中,一种细胞化学可检测的葡萄糖-6-磷酸脱氢酶(G6PD)刺激物质的浓度升高,该物质的性质类似于一种可能的胆碱衍生物二甲基亚甲基铵离子。脑室内(i.c.v.)注射半胱氨酸-3(HC-3)可选择性阻断高亲和力神经元胆碱摄取,抑制脑乙酰胆碱(ACh)合成,并通过对下丘脑胆碱能功能的抑制作用降低SHR的动脉血压。进行这些实验是为了研究中枢给予HC-3对SHR下丘脑和血浆中细胞化学可检测的胆碱样物质含量的影响。用微型泵向14只SHR的侧脑室注入HC-3或生理盐水,持续6天。在第7天,接受HC-3的大鼠下丘脑和血浆中细胞化学可检测物质的浓度显著降低。接受生理盐水的SHR下丘脑浓度为每下丘脑225±95.6×10⁸ G6PD U(范围38.2 - 775),接受HC-3的SHR为1.037±0.45×10⁸ G6PD U(范围0.112 - 3.61)(p < 0.05)。各自的血浆浓度分别为284.9±26 U/ml(范围192 - 374)和72.7±14.7 U/ml(范围24 - 119)(p < 0.05)。这些发现与物理化学证据一致,表明细胞化学可检测物质是一种胆碱衍生物。(摘要截断于250字)

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