Histaminergic neurons appear to provide a variety of signaling mechanisms in the brain. A “neuromodulator” role for histamine has received the most attention. Thus, activation of a small number of tuberomammillary cells is thought to release histamine, which subsequently increases excitability in target cells distributed widely throughout the brain . As mentioned, most of this histamine release is nonsynaptic, implying wide diffusion of the modulator. Such a system is consistent with the characteristics of known histamine receptors, which function through “slow” transmission mechanisms (see Chap. 10) requiring the production of intracellular second messengers (Table 14-2). However, it is becoming clear that neuronal histamine is also capable of providing discrete, fast neurotransmission in the brain. For example, electrical stimulation of the tuberomammillary cells has been shown to evoke fast excitatory postsynaptic potentials in phasically firing supraoptic neurons, effects that are mimicked by application of histamine and blocked by histamine antagonists . These findings imply that, like serotonin (see Chap. 13), histamine may be able to activate both ligand-operated channels and receptors linked to second messengers. The former remain to be identified, however.
asic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition.