Sex Differences in Histamine Receptor Expression in Visceral Afferents of Rat: a Potential Mechanism for Sexual Dimorphism in Visceral Afferent Reflex Function

Abstract

Our previous study has demonstrated a novel sex difference of histamine-mediated neuroexcitability in nodose ganglion neurons (NGNs), highlighting a possible role for histamine in mediating the sex difference in visceral diseases. In the present study, we explored the sex difference in expression of histamine receptors in nodose ganglia and individual NGNs to provide deeper insight into histamine-mediated effects on visceral afferents. Western-blot and RT-PCR showed that H2R and H3R were highly expressed in females vs males and downregulated in OVX females. H1R was equally expressed in both sexes and was not altered in OVX. Immunofluorescence located H2R and H3R in myelinated and unmyelinated NGNs in female rats, however, H3R was mainly localized in nucleus. Single cell PCR indicated that H2R highly distributed in low-threshold and sex-specific myelinated Ah-type NGNs in females. Surprisingly, nearly no H1R was detected in myelinated and unmyelinated NGNs by immunofluorescence, which was further confirmed by single cell PCR. A novel fast inward current with conventional slow inward current induced by histamine was identified in NGNs in females using whole-cell patch. Combination with our previous data, these results further suggest a histamine-mediated sexual dimorphism in visceral afferent reflex. The specific expression profile of histamine receptors and electrophysiology mediated by histamine in low-threshold and sex-specific myelinated Ah-type NGNs in females are probably a potential mechanism for the sexr difference of prevalence and severity of visceral diseases (supported by NSFC 31171122). *These authors contributed equally to this work. Correspondence: B-Y Li (BYL3176033110@163.com)