Rioux F, Kérouac R, St-Pierre S
Neuropeptides. 1983 Jul;3(5):345-54. doi: 10.1016/0143-4179(83)90023-9.
We assessed the influence of various doses of [D-Trp11]-NT on the increase of histaminemia and hematocrit, and decrease of blood pressure, caused by intravenous injections of neurotensin (NT), substance P (SP) and compound 48/80 (C48/80) in anesthetized rats. [D-Trp11]-NT was found to inhibit dose-dependently and selectively the changes of histaminemia, hematocrit and blood pressure caused by NT. Since the highest dose of [D-Trp11]-NT utilized exhibited slight NT-like activity, we tested the possibility that desensitization rather than true pharmacological antagonism was responsible for the inhibitory action of [D-Trp11]-NT toward NT. This hypothesis was verified by evaluating the influence of intravenous infusions of sub-stimulatory and slightly active doses of NT on NT-induced effects. The sub-stimulatory dose (0.1 nmoles kg-1 min-1) as well as a higher dose rate (0.2 nmole kg-1 min-1) of NT were found to inhibit markedly the changes of histaminemia, hematocrit and blood pressure evoked by bolus doses of NT, without altering the effects of C48/80 on the same parameters. These results suggest that the inhibitory action of [D-Trp11]-NT toward NT-induced changes of histaminemia, hematocrit and blood pressure could be the result of receptor desensitization rather than to a true pharmacological antagonism. The results also suggest that the sensitivity of target tissues to exogenous NT could be modulated to some extent by endogenous circulating levels of NT.
我们评估了不同剂量的[D-色氨酸11]-神经降压素（[D-Trp11]-NT）对麻醉大鼠静脉注射神经降压素（NT）、P物质（SP）和48/80化合物（C48/80）所引起的组胺血症增加、血细胞比容升高及血压降低的影响。结果发现，[D-Trp11]-NT能剂量依赖性且选择性地抑制NT所引起的组胺血症、血细胞比容及血压的变化。由于所使用的[D-Trp11]-NT的最高剂量表现出轻微的NT样活性，我们测试了脱敏而非真正的药理拮抗作用是[D-Trp11]-NT对NT产生抑制作用的原因这一可能性。通过评估静脉输注亚刺激剂量和轻微活性剂量的NT对NT诱导效应的影响，这一假设得到了验证。发现NT的亚刺激剂量（0.1纳摩尔·千克-1·分钟-1）以及更高剂量率（0.2纳摩尔·千克-1·分钟-1）能显著抑制大剂量NT所引起的组胺血症、血细胞比容及血压的变化，而不改变C48/80对相同参数的影响。这些结果表明，[D-Trp11]-NT对NT诱导的组胺血症、血细胞比容及血压变化的抑制作用可能是受体脱敏的结果，而非真正的药理拮抗作用。结果还表明，靶组织对外源性NT的敏感性可在一定程度上受到内源性循环NT水平的调节。
