Implications of histaminergic system in brain histamine dysfunction

Abstract

Histamine a signaling molecule synthesized in a variety of cells and is involved in a broad spectrum of functions both in health and disease. It is a hydrophobic molecule composed of an imidazole ring and an amino group connected by two methylene groups. It is synthesized in a wide variety of cells including mast cells, basophils, platelets, enterochromaffin-like cells, endothelial cells and neurons from L-histidine by the enzyme L-histidine decarboxylase. Histamine is believed to stimulate nociceptive afferent fibers in a variety of tissues such as dura mater, heart, joints, jejunum and skin. It activates itch receptors in the skin to produce scratching. Histamine is present in the central nervous system (CNS) of invertebrates, lower vertebrates and mammals and is stored in at least two classes of cells including neurons and mast cells. In the CNS, histamine acts as a key neurotransmitter and involved in the regulation of most of the brain activities in the physiological and pathological states. The cell bodies of the histaminergic neuronal system are concentrated in the tuberomamillary nucleus (TMN) of hypothalamus from which axons reach to innervate almost all regions of the central nervous system from cortex to the spinal cord. Histamine neurons are involved in many functions of central nervous system such as spontaneous locomotion, arousal in wake-sleep cycle, appetite control, seizures, learning and memory, aggressive behavior, emotion, thermoregulation, respiratory and cardiovascular control, neuroendocrine responses, drug sensitization, ischemic lesions, stress, and pain. In this chapter we review the reported actions of histamine in different pathophysiological states of brain. © Springer Science+Business Media B.V. 2010.