Functional pharmacology of H1 histamine receptors expressed in mouse preoptic/anterior hypothalamic neurons.
Functional pharmacology of H1 histamine receptors expressed in mouse preoptic/anterior hypothalamic neurons.
复制标题
小鼠视前/下丘脑前神经元中表达的 H1 组胺受体的功能药理学。
DOI：
10.1111/bph.12286
复制
发表时间：
2013
影响因子：
7.3
通讯作者：
Tabarean,IV
中科院分区：
文献类型：
--
作者：
Tabarean,IV
Background and PurposeHistamine H1receptors are highly expressed in hypothalamic neurons and mediate histaminergic modulation of several brain‐controlled physiological functions, such as sleep, feeding and thermoregulation. In spite of the fact that the mouse is used as an experimental model for studying histaminergic signalling, the pharmacological characteristics of mouse H1receptors have not been studied. In particular, selective and potent H1receptor agonists have not been identified.Experimental ApproachCa2+imaging using fura‐2 fluorescence signals and whole‐cell patch‐clamp recordings were carried out in mouse preoptic/anterior hypothalamic neurons in culture.Key ResultsThe H1receptor antagonists mepyramine and trans‐triprolidine potently antagonized the activation by histamine of these receptors with IC50values of 0.02 and 0.2 μM respectively. All H1receptor agonists studied had relatively low potency at the H1receptors expressed by these neurons. Methylhistaprodifen and 2‐(3‐trifluoromethylphenyl)histamine had full‐agonist activity with potencies similar to that of histamine. In contrast, 2‐pyridylethylamine and betahistine showed only partial agonist activity and lower potency than histamine. The histamine receptor agonist, 6‐[2‐(4‐imidazolyl)ethylamino]‐N‐(4‐trifluoromethylphenyl)heptanecarboxamide (HTMT) had no agonist activity at the H1receptors H1 receptors expressed by mouse preoptic/anterior hypothalamic neurons but displayed antagonist activity.Conclusions and ImplicationsMethylhistaprodifen and 2‐(3‐trifluoromethylphenyl)histamine were identified as full agonists of mouse H1receptors. These results also indicated that histamine H1receptors in mice exhibited a pharmacological profile in terms of agonism, significantly different from those of H1receptors expressed in other species.
