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扇贝(Placopecten magellanicus)中单胺合成与分解代谢的药理学分析。

Pharmacological analysis of monoamine synthesis and catabolism in the scallop, Placopecten magellanicus.

作者信息

Pani A K, Croll R P

机构信息

Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.

出版信息

Gen Pharmacol. 1998 Jul;31(1):67-73. doi: 10.1016/s0306-3623(97)00448-5.

Abstract
  1. The efficacies of various agents that affect monoamine synthesis, oxidation and methylation were evaluated in the scallop, Placopecten magellanicus, through the use of high performance liquid chromatography with electrochemical detection. 2. Central ganglia, labial palps and feet from animals bathed in 10(-5) M or 10(-4) M alpha-methyl-p-tyrosine for 1 day followed by 3-6 day recovery in artificial sea water had significantly reduced concentrations of 3,4-dihydroxyphenylalanine, norepinephrine, epinephrine, dopamine and 3,4-dihydroxyphenylacetic acid. 3. Central ganglia, labial palps and feet from scallops incubated in 10(-5) M or 10(-4) M para-chlorophenylalanine for 1 day followed by a 3-6 day wash in artificial sea water had significantly reduced concentrations of 5-hydroxytryptophan, 5-hydroxytryptamine and 5-hydroxy-3-indoleacetic acid. 4. Monamine oxidase inhibitors (administered at 10(-4) M for 1 day followed by a 2-day recovery) significantly decreased the concentrations of 3,4-dihydroxyphenylalanine and 5-hydroxy-3-indolacetic acid and increased the concentrations of their corresponding precursors in tissues. Deprenyl, a monoamine oxidase type B inhibitor, generally had more potent effects than pargyline, which inhibits monoamine oxidase type B and type A. Clorgyline, a monoamine oxidase type A specific inhibitor, showed few significant effects on the levels of the monoamines or their precursors or metabolites. 5. Bath application of 10(-4) M 3,5-dinitrocatechol, a blocker of catechol-O-methyl transferase, resulted in significant decreases in the concentrations of normetanephrine and metanephrine in nervous and other tissues and increased the levels of their corresponding precursors, dopamine, norepinephrine and epinephrine. 6. Generally, treatments that appeared to directly cause changes in levels of catecholaminergic compounds indirectly resulted in inverse changes in levels of indolaminergic compounds, and vice versa. This suggests an interaction between these transmitter systems. 7. The detection of monoaminergic compounds and dramatic changes in their concentrations following various drug effects strongly suggests the presence of mammalian-type metabolic pathways leading to synthesis and subsequent inactivation of monoamines.
摘要
  1. 通过使用带有电化学检测的高效液相色谱法,在扇贝(Placopecten magellanicus)中评估了各种影响单胺合成、氧化和甲基化的药剂的功效。2. 将动物置于10⁻⁵ M或10⁻⁴ M的α-甲基对酪氨酸中浸泡1天,然后在人工海水中恢复3 - 6天,其中枢神经节、唇瓣和足部的3,4 - 二羟基苯丙氨酸、去甲肾上腺素、肾上腺素、多巴胺和3,4 - 二羟基苯乙酸的浓度显著降低。3. 将扇贝置于10⁻⁵ M或10⁻⁴ M的对氯苯丙氨酸中孵育1天,然后在人工海水中冲洗3 - 6天,其中枢神经节、唇瓣和足部的5 - 羟色氨酸、5 - 羟色胺和5 - 羟基 - 3 - 吲哚乙酸的浓度显著降低。4. 单胺氧化酶抑制剂(以10⁻⁴ M给药1天,然后恢复2天)显著降低了组织中3,4 - 二羟基苯丙氨酸和5 - 羟基 - 3 - 吲哚乙酸的浓度,并增加了其相应前体的浓度。司来吉兰,一种B型单胺氧化酶抑制剂,通常比帕吉林(抑制B型和A型单胺氧化酶)具有更强的作用。氯吉兰,一种A型单胺氧化酶特异性抑制剂,对单胺及其前体或代谢产物的水平几乎没有显著影响。(5) 在浴液中施加10⁻⁴ M的3,5 - 二硝基邻苯二酚(一种儿茶酚 - O - 甲基转移酶的阻滞剂),导致神经组织和其他组织中去甲变肾上腺素和变肾上腺素的浓度显著降低,并增加了其相应前体多巴胺、去甲肾上腺素和肾上腺素的水平。6. 一般来说,那些似乎直接导致儿茶酚胺能化合物水平变化的处理,间接导致了吲哚胺能化合物水平的反向变化,反之亦然。这表明这些递质系统之间存在相互作用。7. 单胺能化合物的检测以及各种药物作用后其浓度的显著变化,强烈表明存在导致单胺合成及随后失活的哺乳动物型代谢途径。

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