New aspects of the role of histamine in cardiovascular function: identification, characterization, and potential pathophysiological importance of H3receptors

Author:

Göthert M.,Schlicker E.,Garbarg M.,Schwartz J.-C.,Hey J. A.,Levi R.

Abstract

As a result of intensive research during several decades, the distribution, function, and pathophysiological role of cardiovascular H1and H2receptors are well known, whereas reports on the occurrence and function of H3receptors in blood vessels and the heart have not become available before the last 7 years (i.e., 4 years after the first description of these receptors in the central nervous system in 1983). The development of selective and potent H3receptor agonists and antagonists was a prerequisite for convenient investigations of cardiovascular H3receptors, which like H1and H2receptors are G-protein coupled but unlike them have not yet been cloned. Both in blood vessels and the heart, H3receptors are located on noradrenergic nerve endings and upon stimulation mediate an inhibition of noradrenaline release. Whereas it remains to be clarified under which conditions the vascular H3receptors may be stimulated by endogenous histamine, those in the heart become activated in the early phases of myocardial ischemia characterized by an increased histamine spillover. The H3receptors in the central nervous system also appear to be of importance for the control of vascular function. Inhibitory presynaptic H3receptors occur on trigeminal sensory C fibres supplying blood vessels in the dura mater. Release of neuropeptides from these fibres induces a neurogenic inflammation, which has been suggested to be involved in the pathogenesis of migraine. An interaction, involving presynaptic H3receptors, between sensory C fibres and mast ceils in close apposition to these fibres plays a role in the control of histamine synthesis in the dura mater. By influencing this regulatory process, H3receptor agonists may limit the extent of the neurogenic inflammation involved in the pathophysiology of migraine.Key words: histamine receptors, H3receptors, presynaptic receptors, noradrenaline release, migraine.

Publisher

Canadian Science Publishing

Subject

Physiology (medical),Pharmacology,General Medicine,Physiology

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