Sun X, Edvinsson L, Hedner T
Department of Pharmacology, University of Göteborg, Sweden.
Pharmacol Toxicol. 1994 Dec;75(6):371-6. doi: 10.1111/j.1600-0773.1994.tb00377.x.
The modulatory effects of alpha-trinositol (D-myo-inositol-1.2.6- trisphosphate; PP 56) on the systemic arterial blood pressor responses induced by neuropeptide Y, preganglionic nerve stimulation, phenylephrine and vasopressin were studied in pithed rats. Intravenous administration (within 2 min.) of alpha-trinositol reduced the neuropeptide Y-induced increase in mean arterial pressure within a defined dose range without altering the heart rate. The influence of alpha-trinositol on the neuropeptide Y-induced pressor response in the presence of non-selective as well as H1- and H2-selective histamine antagonists (diphenhydramine, mepyramine and cimetidine respectively) were investigated. The maximal increase in mean arterial pressure induced by neuropeptide Y as well as the duration of the pressor response was enhanced after nonselective (diphenhydramine) or H1-selective (mepyramine) histamine blockade. The enhancement of the neuropeptide Y-induced pressor response by the H1 specific antagonist mepyramine was significantly more pronounced compared to the H2-selective agent. The exaggerated increase in mean arterial pressure in response to neuropeptide Y after histamine blockade was inhibited by alpha-trinositol to a similar extent as without such pretreatment. We conclude that neuropeptide Y interacts with histamine in the pithed rat and that this action may partially offset the pressor actions of the peptide. The neuropeptide Y-induced pressor responses may be inhibited by alpha-trinositol within a defined dose range indicating that this non-peptide agent may act as a functional inhibitor to neuropeptide Y in vascular tissue.
在脊髓横断大鼠中研究了α-三磷酸肌醇（D-肌醇-1,2,6-三磷酸；PP 56）对神经肽Y、节前神经刺激、去氧肾上腺素和血管加压素诱导的全身动脉血压反应的调节作用。静脉注射（2分钟内）α-三磷酸肌醇在一定剂量范围内可降低神经肽Y诱导的平均动脉压升高，且不改变心率。研究了α-三磷酸肌醇在非选择性以及H1和H2选择性组胺拮抗剂（分别为苯海拉明、美吡拉敏和西咪替丁）存在的情况下对神经肽Y诱导的升压反应的影响。在非选择性（苯海拉明）或H1选择性（美吡拉敏）组胺阻断后，神经肽Y诱导的平均动脉压最大升高以及升压反应的持续时间均增强。与H2选择性拮抗剂相比，H1特异性拮抗剂美吡拉敏对神经肽Y诱导的升压反应的增强作用明显更显著。组胺阻断后对神经肽Y的平均动脉压过度升高被α-三磷酸肌醇抑制的程度与未进行此类预处理时相似。我们得出结论，在脊髓横断大鼠中神经肽Y与组胺相互作用，且这种作用可能部分抵消该肽的升压作用。在一定剂量范围内，α-三磷酸肌醇可抑制神经肽Y诱导的升压反应，表明这种非肽类药物可能在血管组织中作为神经肽Y的功能性抑制剂发挥作用。
