Analysis of histamine as a hair-cell transmitter in the lateral line of Xenopus laevis

The actions of histamine and histamine antagonists on afferent nerve activity were investigated in the lateral line of Xenopus laevis. Histamine (0.002–2.0 mM) had no effect on spontaneous activity or excitatory responses to water motion. In contrast, pyrilamine, an H1 receptor antagonist, suppressed spontaneous activity beginning at 0.01–0.05 mM. Below 0.3 mM the suppression was often preceded by a small excitatory response and responses to high (24–30 dB re threshold), but not low (0–18 dB) levels of water motion were selectively suppressed. Higher concentrations (0.3–2.0 mM) abolished spontaneous activity and suppressed responses at all levels of water motion. Cimetidine, an H2 receptor antagonist, had similar actions but was one-tenth as potent as pyrilamine. Tetrodotoxin (0.001–0.1 μM), which blocks voltage-sensitive Na+ channels, mimicked the suppressive effects of the histamine antagonists. Histamine (2.0 mM) failed to block the actions of pyrilamine (0.1 mM) indicating its effects are mediated through a mechanism other than histamine receptors. In addition, pyrilamine (0.05–0.1 mM) non-selectively suppressed excitation to exogenously applied l-glutamate (1.0–2.0 mM), l-aspartate (1.0–2.0 mM), kainate (0.005–0.01 mM), and quisqualate (0.002–0.005 mM) and altered responses to N-methyl-d-aspartate (0.5–1.0 mM). The results are inconsistent with histamine being a transmitter in the Xenopus lateral line and reveal that the actions of histamine antagonists are nonspecific, possibly due, in part, to blockade of voltage-sensitive Na+ channels.