Fuller R W, Snoddy H D, Perry K W
Life Sci. 1982 Aug 9;31(6):563-70. doi: 10.1016/0024-3205(82)90485-4.
Dopamine concentration in rat heart is normally very low, only a few percent of the concentration of norepinephrine. After treatment of rats with a dopamine beta-hydroxylase inhibitor, 1-cyclohexyl-2-mercapto-imidazole (CHMI), there was a rapid increase in dopamine concentration even before norepinephrine concentration had decreased perceptibility. This accumulation of dopamine was readily measured by liquid chromatography with electrochemical detection. Since the percentage change in dopamine was much greater than the percentage change in norepinephrine, especially at early times, measurement of dopamine accumulation rather than norepinephrine decline was considered as a useful measure of norepinephrine turnover. Drugs that act on noradrenergic receptors and are known to alter norepinephrine turnover were found to alter the rate of dopamine accumulation. Clonidine and guanabenz decreased dopamine accumulation after CHMI, whereas piperoxan (but not prazosin) increased dopamine accumulation after CHMI. Pergolide, a dopamine agonist whose lowering of blood pressure and cardiac rate has been suggested to be due to suppression of neurogenic release or norepinephrine, also decreased dopamine accumulation after CHMI. The results suggest that measuring dopamine accumulation may have advantages over measuring norepinephrine disappearance after dopamine beta-hydroxylase inhibition as an indicator of norepinephrine turnover in heart.
大鼠心脏中的多巴胺浓度通常非常低,仅为去甲肾上腺素浓度的百分之几。用多巴胺β-羟化酶抑制剂1-环己基-2-巯基咪唑(CHMI)处理大鼠后,甚至在去甲肾上腺素浓度尚未明显下降之前,多巴胺浓度就迅速升高。多巴胺的这种积累很容易通过液相色谱-电化学检测来测量。由于多巴胺的百分比变化远大于去甲肾上腺素的百分比变化,尤其是在早期,因此测量多巴胺的积累而非去甲肾上腺素的下降被认为是衡量去甲肾上腺素周转率的一种有用方法。已知作用于去甲肾上腺素能受体并能改变去甲肾上腺素周转率的药物被发现会改变多巴胺积累的速率。可乐定和胍那苄在CHMI后降低了多巴胺的积累,而哌罗克生(但不是哌唑嗪)在CHMI后增加了多巴胺的积累。培高利特是一种多巴胺激动剂,其降低血压和心率的作用被认为是由于抑制神经源性释放或去甲肾上腺素,它在CHMI后也降低了多巴胺的积累。结果表明,作为心脏中去甲肾上腺素周转率的指标,测量多巴胺的积累可能比测量多巴胺β-羟化酶抑制后去甲肾上腺素的消失更具优势。