Premium
Functional pharmacology of H 1 histamine receptors expressed in mouse preoptic/anterior hypothalamic neurons
Author(s) -
Tabarean I V
Publication year - 2013
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12286
Subject(s) - histaminergic , agonist , histamine , histamine receptor , receptor , medicine , endocrinology , histamine h3 receptor , dimaprit , histamine h1 receptor , pharmacology , chemistry , biology , antagonist
Background and Purpose Histamine H 1 receptors 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 H 1 receptors have not been studied. In particular, selective and potent H 1 receptor agonists have not been identified. Experimental Approach Ca 2+ imaging using fura‐2 fluorescence signals and whole‐cell patch‐clamp recordings were carried out in mouse preoptic/anterior hypothalamic neurons in culture. Key Results The H 1 receptor antagonists mepyramine and trans‐triprolidine potently antagonized the activation by histamine of these receptors with IC 50 values of 0.02 and 0.2 μM respectively. All H 1 receptor agonists studied had relatively low potency at the H 1 receptors 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 H 1 receptors H1 receptors expressed by mouse preoptic/anterior hypothalamic neurons but displayed antagonist activity. Conclusions and Implications Methylhistaprodifen and 2‐(3‐trifluoromethylphenyl)histamine were identified as full agonists of mouse H 1 receptors. These results also indicated that histamine H 1 receptors in mice exhibited a pharmacological profile in terms of agonism, significantly different from those of H 1 receptors expressed in other species.