Additional sites of HA action

There is ample evidence indicating that HA can induce responses which are not mediated by any of the four GPCRs discussed presently, although the significance of these remains uncertain. HA can modulate NMDA receptor activity by an action at the polyamine binding site (Brown et al. 2001). HA can also act on ion channels directly in invertebrates (Brown et al. 2001; Gisselmann et al. 2002; Zheng et al. 2002). In mammals, there is evidence for histaminergic ionotropic transmission which may involve both excitatory and inhibitory receptors (Hatton and Yang 1996, 2001), but these receptors have not yet been isolated or characterized. There may also be additional HA-activated GPCRs yet to be discovered and characterized.

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