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LY-141865和阿扑吗啡对大鼠肾脏中突触前多巴胺受体的选择性激活以及刺激参数在多巴胺作用中的影响。

Selective activation by LY-141865 and apomorphine of presynaptic dopamine receptors in the rat kidney and influence of stimulation parameters in the action of dopamine.

作者信息

Lokhandwala M F, Steenberg M L

出版信息

J Pharmacol Exp Ther. 1984 Jan;228(1):161-7.

PMID:6694099
Abstract

The presence and physiological role of presynaptic dopamine receptors in the isolated-perfused rat kidney was assessed by determining the effects of several agonists and antagonists on the release of [3H]norepinephrine elicited during periarterial nerve stimulation. In the presence of cocaine, dopamine caused a concentration-dependent inhibition of stimulus-induced release of [3H]norepinephrine at 0.5 and 2 Hz. Phentolamine as well as sulpiride caused partial antagonism of the inhibitory action of dopamine at 0.5 Hz (20 sec) and a combination of both of these agents was required to completely antagonize the action of dopamine. The inhibition of [3H]norepinephrine release caused by dopamine at 2 Hz (20 sec) was completely antagonized by sulpiride alone and phentolamine had no effect on the inhibitory action of dopamine. These results suggest that dopamine-induced inhibition of norepinephrine release depends on the conditions of stimulation, i.e., during lower frequencies of sympathetic nerve stimulation, inhibition occurs by simultaneous activation of both presynaptic dopamine receptors as well as alpha adrenoceptors, whereas only presynaptic dopamine receptors are responsible for the inhibition of neurotransmitter release caused by dopamine at the higher frequency of nerve stimulation. The dopamine receptor agonists apomorphine and LY-141865 caused concentration-dependent inhibition of [3H]norepinephrine release elicited during periarterial nerve stimulation at 0.5 Hz, which was antagonized by sulpiride but not by phentolamine, suggesting that selective stimulation of presynaptic dopamine receptors accounted for inhibitory actions of these compounds. In the presence of cocaine, norepinephrine also inhibited stimulus-induced release of [3H]norepinephrine at 0.5 Hz, which could be antagonized by phentolamine but not sulpiride.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

通过测定几种激动剂和拮抗剂对动脉周围神经刺激期间诱发的[3H]去甲肾上腺素释放的影响,评估了离体灌注大鼠肾脏中突触前多巴胺受体的存在及其生理作用。在可卡因存在的情况下,多巴胺在0.5和2 Hz时对刺激诱导的[3H]去甲肾上腺素释放产生浓度依赖性抑制。酚妥拉明和舒必利在0.5 Hz(20秒)时对多巴胺的抑制作用产生部分拮抗作用,需要这两种药物联合使用才能完全拮抗多巴胺的作用。多巴胺在2 Hz(20秒)时引起的[3H]去甲肾上腺素释放抑制被单独的舒必利完全拮抗,酚妥拉明对多巴胺的抑制作用没有影响。这些结果表明,多巴胺诱导的去甲肾上腺素释放抑制取决于刺激条件,即在较低频率的交感神经刺激期间,抑制是通过突触前多巴胺受体和α肾上腺素能受体同时激活而发生的,而在较高频率的神经刺激下,只有突触前多巴胺受体负责多巴胺引起的神经递质释放抑制。多巴胺受体激动剂阿扑吗啡和LY-141865在0.5 Hz的动脉周围神经刺激期间对诱发的[3H]去甲肾上腺素释放产生浓度依赖性抑制,这被舒必利拮抗但未被酚妥拉明拮抗,表明突触前多巴胺受体的选择性刺激解释了这些化合物的抑制作用。在可卡因存在的情况下,去甲肾上腺素在0.5 Hz时也抑制刺激诱导的[3H]去甲肾上腺素释放,这可被酚妥拉明拮抗但不能被舒必利拮抗。(摘要截短于250字)

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