Introduction

Histamine [2-(4-imidazolyl)ethylamine, HA] is an endogenous biogenic amine synthesized in and released from several kinds of cells, and involved in many kinds of biological signalling (Uvnas 1991). Mast cells (a family of bone marrow-derived secretory cells) store much of the body's HA in very high concentrations. These cells respond with HA release to a myriad of diverse signals (including tissue damage, antigen exposure, and some kinds of drugs), yet the significance of mast cell HA under strictly physiological conditions remains unknown. In contrast, HA in the gastric mucosa is stored in and released from specialized cells resembling enterochromaffin cells, where it plays a vital physiological role as a mediator of normal gastric acid secretion. HA is also abrain neurotransmitter (Brown etal. 2001; Hough 1999). Located in the tuberomammillary nucleus of the hypothalamus, histaminergic neurones project widely throughout the brain and, as discussed in this chapter, are thought to participate in several brain functions.

This chapter reviews information about the protein biosensors which recognize HA and initiate the transduction of extracellular HA levels into an incredible repertoire of biological responses. Related topics which are also discussed include the drugs known to act on these receptors, and the physiological and pathological significance of the receptors. Many earlier reviews on HA receptors have been published (Hill etal. 1997; Leurs etal. 1998; Hough 2001; Arrang et al. 1995; Leurs et al. 1995b; Hill 1992) and the reader is also referred to broader reviews of HA (Brown et al. 2001; Hough 1999; Onodera et al. 1994; Schwartz et al. 1991; Hough 1988; Silver etal. 1996; Barke and Hough 1993). Topics such as the synthesis, storage, release, and metabolism of HA (and drugs acting on these mechanisms) are not discussed in the present chapter, but are covered in some of these other reviews.

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