Tyler B M, Groshan K, Cusack B, Richelson E
Neuropsychopharmacology Research, Mayo Foundation for Medical and Educational Research, Jacksonville, FL 32224, USA.
Brain Res. 1998 Mar 16;787(1):78-84. doi: 10.1016/s0006-8993(97)01479-0.
The present study describes in vivo experiments in the rat addressing the role of levocabastine, and two other specific histamine H1 antagonists, diphenhydramine and pyrilamine, at neurotensin (NT)-mediated hypothermia and antinociception (hotplate). Levocabastine given i.p. or microinjected directly into the periaqueductal gray (PAG) did not cause antinociception or hypothermia. This indicates that despite the results with the recently-cloned levocabastine-sensitive NT receptors (NTR) in the rat (NTR-2) and mouse (NTRL), levocabastine by itself does not mediate either hypothermia or antinociception at NT receptors. However, pretreatment with 5 or 50 microg/kg of levocabastine or 5 microg/kg diphenhydramine all caused over a three-fold reduction in NT-mediated antinociception. Higher doses (500 or 5000 microg/kg) of levocabastine did not cause any antagonism of NT-mediated antinociception. All three antihistamines did not affect NT-mediated hypothermia. In addition, histamine H1 pathways are not involved in NT-mediated antinociception, as pretreatment with the much more potent histamine H1 antagonist pyrilamine did not affect antinociception mediated by NT. Therefore, these data may suggest the presence of yet unidentified NTR subtypes responsible for NT-mediated hypothermia and antinociception.
本研究描述了在大鼠体内进行的实验，探讨了左卡巴斯汀以及另外两种特异性组胺H1拮抗剂苯海拉明和吡苄明在神经降压素（NT）介导的体温过低和抗伤害感受（热板法）中的作用。腹腔注射或直接微量注射到导水管周围灰质（PAG）中的左卡巴斯汀不会引起抗伤害感受或体温过低。这表明，尽管最近在大鼠（NTR-2）和小鼠（NTRL）中克隆出了对左卡巴斯汀敏感的NT受体（NTR），但左卡巴斯汀本身并不能在NT受体上介导体温过低或抗伤害感受。然而，用5或50微克/千克的左卡巴斯汀或5微克/千克的苯海拉明预处理均导致NT介导的抗伤害感受降低了三倍以上。更高剂量（500或5000微克/千克）的左卡巴斯汀不会对NT介导的抗伤害感受产生任何拮抗作用。所有三种抗组胺药均不影响NT介导的体温过低。此外，组胺H1途径不参与NT介导的抗伤害感受，因为用更强效的组胺H1拮抗剂吡苄明预处理不会影响NT介导的抗伤害感受。因此，这些数据可能表明存在尚未确定的负责NT介导的体温过低和抗伤害感受的NTR亚型。
