title: Sex- and afferent-specific differences in histamine receptor expression in vagal afferents of rats: A potential mechanism for sexual dimorphism in prevalence and severity of asthma.
abstract: The incidence of asthma is more common in boys than in girls during the childhood, and more common in premenopausal female than age-matched males. Our previous study demonstrated a gender difference in histamine-mediated neuroexcitability in nodose ganglia neurons (NGNs), highlighting a possibility of histamine-mediated gender difference in asthma via visceral afferent function. In the present study, we aimed to explore the gender difference in expression profiles of histamine receptors (HRs) in nodose ganglia (NG) and individual identified NGNs to provide deeper insights into the mechanisms involved in sexual dimorphism of asthma. Western-blot and SYBR green RT-PCR showed that H2R and H3R were highly expressed in NG of females compared with males and downregulated in ovariectomized females. H1R was equally expressed in NG of both sexes and not altered by ovariectomy. Furthermore, this highly expressive H2R and H3R were distributed in both myelinated and unmyelinated NGNs isolated from adult female rats by immunofluorescence and single-cell RT-PCR. H3R widely distributed in all tested neuron subtypes and its expression did not show significant difference among neuron subtypes. H2R was widely and highly expressed in low-threshold and sex-specific subpopulation of myelinated Ah-types compared with myelinated A- and unmyelinated C-type NGNs. Unexpectedly, weak expression of H1R was detected in both myelinated and unmyelinated NGNs by immunofluorescence, which was further confirmed by single-cell RT-PCR. Our results suggest that the sexual dimorphism in the expression of H2R and H3R in vagal afferents very likely contributes, at least partially, to the gender difference in prevalence and severity of asthma.
authors.affiliation: Department of Pharmacology, Harbin Medical University, Harbin, China.
authors.forename: J N
authors.initials: JN
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Harbin Medical University, Harbin, China; Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, Harbin Medical University, Harbin, China.
authors.forename: X L
authors.initials: XL
authors.lastname: Li
authors.affiliation: Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, Harbin Medical University, Harbin, China.
authors.forename: J
authors.initials: J
authors.lastname: He
authors.affiliation: Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, Harbin Medical University, Harbin, China.
authors.forename: J X
authors.initials: JX
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, Harbin Medical University, Harbin, China.
authors.forename: M
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, Harbin Medical University, Harbin, China.
authors.forename: X B
authors.initials: XB
authors.lastname: Liang
authors.affiliation: Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, Harbin Medical University, Harbin, China.
authors.forename: S Y
authors.initials: SY
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, Harbin Medical University, Harbin, China.
authors.forename: M N
authors.initials: MN
authors.lastname: Ma
authors.affiliation: Department of Pharmacology, Harbin Medical University, Harbin, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cerebral Surgery, Harbin Municipal First Hospital, Harbin, China.
authors.forename: Y B
authors.initials: YB
authors.lastname: Wang
authors.affiliation: Riley Heart Research Center, Division of Pediatric Cardiology, Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, USA.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Harbin Medical University, Harbin, China; Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, Harbin Medical University, Harbin, China. Electronic address: qiaogf88@163.com.
authors.forename: G F
authors.initials: GF
authors.lastname: Qiao
authors.affiliation: Department of Pharmacology, Harbin Medical University, Harbin, China. Electronic address: liby@ems.hrbmu.edu.cn.
authors.forename: B Y
authors.initials: BY
authors.lastname: Li
mesh_terms: D000200:Action Potentials; D000344:Afferent Pathways / Q000378:metabolism; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000378:metabolism; D005260:Female; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D009620:Nodose Ganglion / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011968:Receptors, Histamine / Q000378:metabolism*; D012737:Sex Factors
chemical_list: D011968:Receptors, Histamine
keywords: asthma; electrophysiology; gender difference; histamine receptor; vagal afferents