Bealer S L
Department of Physiology and Biophysics, University of Tennessee, Memphis.
J Pharmacol Exp Ther. 1993 Feb;264(2):734-8.
These experiments evaluated norepinephrine (NE) release evoked by histamine (HA) in the paraventricular nucleus/anterior hypothalamic (PV/AH) region of conscious rats. In vivo microdialysis techniques were used to estimate extracellular NE concentrations in the PV/AH before, during and after perfusing the microdialysis probes with artificial cerebrospinal fluid containing HA (0, 1, 3 or 10 mg of HA per ml of artificial cerebrospinal fluid). Administration of HA through the microdialysis probe resulted in a significant, dose-related increase in dialysate NE concentration, which returned to control values after HA perfusion. Blood pressure and heart rate were not altered during perfusion with these concentrations of HA. The increase in NE was attenuated by administration of a specific H1 receptor antagonist, chlorpheniramine, but was not altered consistently by treatment with the H2 receptor antagonist, cimetidine. Furthermore, extracellular NE increased when perfusate contained the specific H1 receptor agonist, 2-thiazolyethylamine, but was not increased by similar administration of the H2 receptor agonist, dimaprit. These data demonstrate that HA releases NE in the PV/AH brain region of the conscious rat primarily by activation of H1 receptors. This finding supports an interaction between HA and NE neurons in the hypothalamus.
这些实验评估了组胺(HA)诱发清醒大鼠室旁核/下丘脑前部(PV/AH)区域去甲肾上腺素(NE)释放的情况。采用体内微透析技术来估计在用含HA(每毫升人工脑脊液含0、1、3或10毫克HA)的人工脑脊液灌注微透析探针之前、期间及之后PV/AH区域细胞外NE的浓度。通过微透析探针给予HA导致透析液中NE浓度显著且呈剂量相关增加,HA灌注后其恢复至对照值。在用这些浓度的HA灌注期间,血压和心率未发生改变。给予特异性H1受体拮抗剂氯苯那敏可减弱NE的增加,但用H2受体拮抗剂西咪替丁治疗并未使其持续改变。此外,当灌注液含有特异性H1受体激动剂2-噻唑乙胺时细胞外NE增加,但给予类似剂量的H2受体激动剂二甲双胍未使其增加。这些数据表明,HA主要通过激活H1受体在清醒大鼠的PV/AH脑区释放NE。这一发现支持了下丘脑内HA与NE神经元之间的相互作用。