Ralevic V, Edvinsson L, Burnstock G
Department of Anatomy, University College London, UK.
Acta Physiol Scand. 1994 Jul;151(3):309-17. doi: 10.1111/j.1748-1716.1994.tb09750.x.
The effect of the neuropeptide Y antagonist D-myo-inositol-1,2, 6-trisphosphate (alpha-trinositol) was tested against modulatory actions mediated by neuropeptide Y in the isolated rat mesenteric arterial bed. Neuropeptide Y (1 and 10 nM) had no direct postjunctional effects, but augmented vasoconstrictor responses to noradrenaline and to sympathetic nerve stimulation to an extent which was greater with the higher concentration of neuropeptide Y. The augmenting effect of neuropeptide Y at 1 nM on vasoconstriction induced by lower doses of noradrenaline was antagonized by alpha-trinositol (1 microM), producing a shift to the right of the dose-response curve. A lower concentration of alpha-trinositol (0.1 microM) had no inhibitory effect on responses to noradrenaline. Augmentation by the higher concentration of neuropeptide Y (10 nM) of noradrenaline-induced vasoconstriction was not affected by alpha-trinositol at concentrations of up to 10 microM. alpha-Trinositol did not significantly antagonize neuropeptide Y-induced augmentation of vasoconstrictor responses to sympathetic nerve stimulation. alpha-Trinositol alone did not affect vasoconstrictor responses to noradrenaline, potassium, or to sympathetic nerve stimulation. In the raised-tone preparation (tone raised with methoxamine) in the presence of guanethidine (5 microM) to block sympathetic neuro-transmission, perivascular nerve stimulation caused vasodilatation due to activation of sensory-motor nerves. Neuropeptide Y inhibited sensory-motor nerve induced vasodilatation in a concentration-dependent manner but this was not affected by alpha-trinositol (1 microM). These results suggest that alpha-trinositol can be a useful functional antagonist of neuropeptide Y-induced augmentation of vasoconstrictor responses to noradrenaline in the rat mesenteric arterial bed.(ABSTRACT TRUNCATED AT 250 WORDS)
在离体大鼠肠系膜动脉床中，测试了神经肽Y拮抗剂D - 肌醇 - 1,2,6 - 三磷酸（α - 三肌醇）对抗由神经肽Y介导的调节作用。神经肽Y（1和10 nM）无直接的节后效应，但增强了对去甲肾上腺素和交感神经刺激的血管收缩反应，且神经肽Y浓度越高，增强程度越大。1 nM神经肽Y对较低剂量去甲肾上腺素诱导的血管收缩的增强作用被α - 三肌醇（1 μM）拮抗，使剂量 - 反应曲线右移。较低浓度的α - 三肌醇（0.1 μM）对去甲肾上腺素反应无抑制作用。高达10 μM浓度的α - 三肌醇不影响较高浓度神经肽Y（10 nM）对去甲肾上腺素诱导的血管收缩的增强作用。α - 三肌醇对神经肽Y诱导的对交感神经刺激的血管收缩反应增强作用无明显拮抗作用。单独使用α - 三肌醇不影响对去甲肾上腺素、钾或交感神经刺激的血管收缩反应。在存在胍乙啶（5 μM）以阻断交感神经传递的升压制剂（用甲氧明升高张力）中，血管周围神经刺激因感觉 - 运动神经激活而导致血管舒张。神经肽Y以浓度依赖方式抑制感觉 - 运动神经诱导的血管舒张，但这不受α - 三肌醇（1 μM）影响。这些结果表明，α - 三肌醇可能是大鼠肠系膜动脉床中神经肽Y诱导的对去甲肾上腺素血管收缩反应增强的有效功能性拮抗剂。（摘要截短于250字）
