Pharmacological approach of histamine H3 receptors: use of arterial and bronchiolar perfusion technique
Oudart, N.; Kim, L.E.; Burgaud, J.L.
Annales Pharmaceutiques Francaises 54(5): 217-222
1996
ISSN/ISBN: 0003-4509 PMID: 8953796 Document Number: 460216
The actions of histamine were believed to be mediated by H1 and H2 receptors, until the discovery of a novel class named H3 in the central nervous system. Initially identified as presynaptic autoreceptors, now, evidence has been obtained drawing that H3 receptors are also located on non histaminergic neurons in the brain and in peripheral organs. In the present study, H3 responses are studied on arterial and bronchiolar segments perfused at constant rate. In the rabbit middle cerebral artery (MCA), the endothelium-dependent relaxation to (R)-alpha-methylhistamine (an agonist H3) was competitively antagonized by thioperamide (an H3 antagonist). This relaxation is endothelium-dependent, involving both a prostanoid, probably prostacyclin, and an endothelium-derived relaxing factor: the nitric oxide. In guinea-pig perfused bronchioles (R)-alpha-methylhistamine induces an epithelium dependent relaxation via the release of metabolite(s) of arachidonic acid. Theses results indicate that H3 sites could exist in the rabbit cerebral arteries and in the guinea-pig bronchiole. Furthermore, the vasorelaxant and the bronchorelaxant effects of (R)-alpha-methylhistamine suggest that H3 agonists may constitute a novel approach for the treatment of diseases as asthma, for example.