Smit J, Coppes R P, van Tintelen E J, Roffel A F, Zaagsma J
Department of Molecular Pharmacology, University Centre for Pharmacy, University of Groningen, The Netherlands.
Naunyn Schmiedebergs Arch Pharmacol. 1997 Feb;355(2):256-60. doi: 10.1007/pl00004940.
The effects of intra-arterial injection of different doses of the selective histamine H3-receptor agonist R-alpha-methylhistamine and the selective histamine H3-receptor antagonist thioperamide on basal and electrically evoked noradrenaline overflow in the portal vein as well as on mean arterial pressure (MAP) and heart rate (HR) were investigated in permanently instrumented freely moving rats. R-alpha-Methylhistamine (0.01, 0.1 and 1 mumol/kg) inhibited the evoked noradrenaline overflow up to 43%, the ED50 value being 0.013 mumol/kg. Thioperamide (0.1, 0.5 and 1.0 mumol/kg) antagonized the effect of 1.0 mumol/kg R-alpha-methylhistamine dose-dependently, evoked overflow returning to control values at 1.0 mumol/kg of the antagonist; thioperamide alone had no effect on electrically evoked noradrenaline overflow. Basal noradrenaline levels, blood pressure and heart rate were not at all influenced by R-alpha-methylhistamine and thioperamide, alone or in combination. The results clearly show the presence of prejunctional histamine H3-receptors inhibiting the electrically evoked noradrenaline overflow from vascular sympathetic nerve terminals in the portal vein of freely moving rats.
在永久性植入仪器的自由活动大鼠中，研究了动脉内注射不同剂量的选择性组胺H3受体激动剂R-α-甲基组胺和选择性组胺H3受体拮抗剂硫代哌酰胺对门静脉基础和电诱发去甲肾上腺素溢出以及平均动脉压（MAP）和心率（HR）的影响。R-α-甲基组胺（0.01、0.1和1 μmol/kg）抑制诱发的去甲肾上腺素溢出高达43%，ED50值为0.013 μmol/kg。硫代哌酰胺（0.1、0.5和1.0 μmol/kg）剂量依赖性地拮抗1.0 μmol/kg R-α-甲基组胺的作用，当拮抗剂剂量为1.0 μmol/kg时，诱发的溢出恢复到对照值；单独使用硫代哌酰胺对电诱发的去甲肾上腺素溢出没有影响。单独或联合使用R-α-甲基组胺和硫代哌酰胺对基础去甲肾上腺素水平、血压和心率均无影响。结果清楚地表明，在自由活动大鼠的门静脉中，存在抑制血管交感神经末梢电诱发去甲肾上腺素溢出的突触前组胺H3受体。
