Lecklin A, Etu-Seppälä P, Stark H, Tuomisto L
Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland.
Brain Res. 1998 May 18;793(1-2):279-88. doi: 10.1016/s0006-8993(98)00186-3.
The actions of intracerebroventricularly-infused histamine and selective histamine H1, H2 and H3 receptor agonists on food and water intake and urine flow were studied in rats. It was found that 100-800 nmoles of histamine significantly suppressed feeding. The H1 agonist 2-(3- trifluoromethylphenyl)histamine (FMPH) decreased food intake, whereas the H2 agonist dimaprit was without effect. Histamine- and FMPH-induced suppressions of feeding were attenuated by blockade of H1 but not by H2 receptors. The results clearly demonstrate that activation of brain H1 receptors decreases food intake. In subsequent studies, we found that both metoprine and thioperamide, which increase histaminergic activity through different mechanisms, also reduced food intake. This finding indicates that the brain histaminergic system is associated with feeding behavior. The same is true with body water homeostasis. Histamine caused a long-lasting diuresis. Also dimaprit and metoprine increased urine flow and the blockade of H2 receptors abolished the diuretic responses to histamine and dimaprit. On the other hand, the H3 agonist (R)-alpha-methylhistamine elicited drinking and this effect could be prevented by thioperamide pretreatment. The results imply that activation of H3 receptors predominantly provokes drinking, whereas central H2 receptors mediate the diuretic effect of histamine.
研究了脑室内注射组胺及选择性组胺H1、H2和H3受体激动剂对大鼠食物和水摄入以及尿流的影响。发现100 - 800纳摩尔的组胺显著抑制进食。H1激动剂2 - (3 - 三氟甲基苯基)组胺(FMPH)可减少食物摄入，而H2激动剂二甲双胍则无此作用。组胺和FMPH引起的进食抑制可被H1受体阻断所减弱，但不能被H2受体阻断所减弱。结果清楚地表明，脑H1受体的激活会减少食物摄入。在随后的研究中，我们发现甲氧氯普胺和硫代哌啶酰胺通过不同机制增加组胺能活性，也能减少食物摄入。这一发现表明，脑组胺能系统与进食行为有关。身体水稳态也是如此。组胺可引起持久的利尿作用。二甲双胍和甲氧氯普胺也增加尿流，H2受体阻断可消除对组胺和二甲双胍的利尿反应。另一方面，H3激动剂(R)-α-甲基组胺引起饮水，这种作用可通过硫代哌啶酰胺预处理来预防。结果表明，H3受体的激活主要引发饮水，而中枢H2受体介导组胺的利尿作用。
