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  • It is well known that histamine

    2022-05-19

    It is well known that histamine functions not only as an inflammation mediator but also as an aminergic neurotransmitter or neuromodulator. Histaminergic neurons [27], [28] and histamine receptor subtypes (H1R [29] and H3R [30]) are widely existed in mammalian central olfactory system. Histamine regulates the activity of interneurons in olfactory bulb through the activation of H1R and H2R [31], and also modulates depolarization-evoked [3H]-noradrenaline release from olfactory bulb slices by stimulation of H3R [9]. These results suggest that histamine may affect the central olfactory system through H1R, H2R, and H3R. However, knowledge about the role of histamine in peripheral olfactory system is limited. Electrophysiological studies on the ORNs of lobster have suggested that histamine acts as an inhibitory transmitter [32], [33]. Histamine suppresses Flurbiprofen invasion of olfactory axon terminals, and the suppression can be blocked by cimetidine [34]. Thus, evidence has been accumulating that histamine and its receptors (H1R, H2R, and H3R) are involved in the regulation of the function of mammalian central olfactory system and the peripheral olfactory system of lobster, but their function in mammalian peripheral olfactory system has not been reported. The results of the present study demonstrated that H1R, H2R, and H3R are strongly expressed in rat ORNs. Mammalian ORNs form the primary elements of the olfactory system. The specific localization of these receptor subtypes in OE suggests that histamine, may also play an important role in olfactory transmission in addition to its contribution to nasal symptoms (nasal itch, sneezing, rhinorrhea, and congestion). H1R, H2R and H3R are localized anatomically in the primate retina [35], [36]. In dark-adapted baboon retinas, histamine decreases the rate of maintained firing and the light sensitivity of retinal ganglion cells with sustained and transient ON responses [37]. Stimulation of H3R increases the delayed rectifier component of the voltage-dependent potassium conductance in ON bipolar cells of macaque retinas, hyperpolarizing the cells by 5 mV, on average [38]. The mRNA expression and immunoreactivity staining for H1R, H2R, and H3R have also been observed in spiral ganglion cells in rat cochlea and these receptors may play a physiological role in neurotransmission of cochlea [39], [40]. Taking into account current results of H1R, H2R, and H3R in retinas and cochlea, we speculate that H1R, H2R, and H3R may also play a role in OE. It was previously demonstrated that levocetirizine, a potent second-generation nonsedative H1-antagonist, could improve the loss of smell in persistent allergic rhinitis patients, which is not correlated with the improvement of nasal obstruction [41]. Furthermore, electroencephalogram spike was found at the olfactory bulb after histamine application into the nasal cavity [42]. In this study, our results demonstrated for the first time the expression and localization of H1R, H2R, and H3R in OE. The results from previous investigations and our current study indicate that histamine may play a physiological role in olfactory transmission and could potentially be one important further mediator responsible for olfactory dysfunction in patients with allergic rhinitis. There are some limitations of the present study. We used Sprague-Dawley rats in this study because of the difficulties in obtaining and analyzing human OE due to both technical and ethical issues. In this study, we demonstrated that H1R, H2R, and H3R are specifically expressed in ORNs. Although the exact function of histamine receptors in ORNs remains largely unclear, we speculate that they play an important role in the regulation of olfactory transmission. In addition, increased nasal histamine in patients with allergic rhinitis could have some physiopathological role in olfactory dysfunction. Further electrophysiological and animal studies of allergic rhinitis are needed to clarify the functions of histamine receptors in OE.