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

Li, J.N.; Li, X.L.; He, Jingyun; Wang, J.X.; Zhao, Miao; Liang, Xiao; Zhao, S.Y.; Ma, Meina; Liu, Y.; Wang, Y.B.; Chen, H.; Qiao, Guofu; Li, B.Y.

doi:10.1016/j.neuroscience.2015.06.049

Cited by 27 publications

(12 citation statements)

References 37 publications

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“…To answer this question, the single-cell real time-polymerase chain reaction (RT-PCR) was performed on electrophysiologically 14 and morphologically 26 identified A-, Ah-, and C-type BRNs isolated from adult female rats. 23 As shown in Figure 2C and 2D, all neuronal subtypes expressed both AT 1 R and AT 2 R, whereas the averaged expression level of AT 1 R was ≈4× to 5× higher in A-type neurons than that in Ah-or C-type neurons, and AT 2 R expression level was ≈7-fold higher in Ah-type neurons compared with A-or C-type neurons.…”

Section: Afferent-specific Expression Of At 1 R and At 2 Rmentioning

confidence: 75%

“…19,20 Ah-type BRNs were rarely found in adult male rats and exhibited an excitability profile that was strongly influenced by circulating sex hormones 3,18,21 and neurotransmitters. 22,23 Therefore, we speculated that the sex difference and afferent-specificity of AT 2 R expression in myelinated Ah-type BRNs may be greatly involved in the baroreflex afferent function of female rats.…”

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confidence: 99%

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Unique Expression of Angiotensin Type-2 Receptor in Sex-Specific Distribution of Myelinated Ah-Type Baroreceptor Neuron Contributing to Sex-Dimorphic Neurocontrol of Circulation

Yang

Zhou

et al. 2016

Hypertension

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T he sex difference in blood pressure (BP) has long been recognized between premenopausal women and agedmatched men.1 Women are protected from most cardiovascular events compared with age-matched men before menopause, and postmenopausal women are at increased risk of cardiovascular complications compared with premenopausal women. 2 The pathophysiological mechanisms have been extensively explored, and increasing evidences have shown that the female hormone is one of the major mechanisms contributing to the above phenomena.3 Several studies have demonstrated the importance of the interaction between sex hormones and the renin-angiotensin system in regulating cardiovascular function and BP. 4,5 Angiotensin-II (Ang-II) is a key player in the development of hypertension. Ang-II type-1 (AT 1 R) and type-2 (AT 2 R) receptors play opposite roles in BP regulation, 6,7 with AT 2 R exerting a cardioprotective action in essential hypertension. 8 Early study demonstrates that AT 2 R provides a major clue for solving the mystery of sex differences in AT 2 R-mediated vasodilation 9 and hypertension. 10 However, the majority of researches on hypertension to date has been conducted in male animals and focused largely on the target organs, such as the heart, blood vessels, and kidney. The sex differences in neurocontrol of circulation at baroreflex level have almost been neglected although AT 1 R or AT 2 R has been identified in nodose ganglia (NG) or nucleus of tractus solitary (NTS). 11,12 Recent literatures have shown that adult female rats express Abstract-This study aims to understand the special expression patterns of angiotensin-II receptor (AT 1 R and AT 2 R) in nodose ganglia and nucleus of tractus solitary of baroreflex afferent pathway and their contribution in sex difference of neurocontrol of blood pressure regulation. In this regard, action potentials were recorded in baroreceptor neurons (BRNs) using whole-cell patch techniques; mRNA and protein expression of AT 1 R and AT 2 R in nodose ganglia and nucleus of tractus solitary were evaluated using real time-polymerase chain reaction, Western blot, and immunohistochemistry at both tissue and single-cell levels. The in vivo effects of 17β-estradiol on blood pressure and AT 2 R expression were also tested. The data showed that AT 2 R, rather than AT 1 R, expression was higher in female than age-matched male rats. Moreover, AT 2 R was downregulated in ovariectomized rats, which was restored by the administration of 17β-estradiol. Single-cell real time-polymerase chain reaction data indicated that AT 2 R was uniquely expressed in Ah-type BRNs. Functional study showed that long-term administration of 17β-estradiol significantly alleviated the blood pressure increase in ovariectomized rats. Electrophysiological recordings showed that angiotensin-II treatment increased the neuroexcitability more in Ah-than C-type BRNs, whereas no such effect was observed in A-types. In addition, angiotensin-II treatment prolonged action potential duration, which was not further changed...

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Section: Afferent-specific Expression Of At 1 R and At 2 Rmentioning

confidence: 75%

mentioning

confidence: 99%

Unique Expression of Angiotensin Type-2 Receptor in Sex-Specific Distribution of Myelinated Ah-Type Baroreceptor Neuron Contributing to Sex-Dimorphic Neurocontrol of Circulation

Yang

Zhou

et al. 2016

Hypertension

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“…From this observation, the conclusion could not be drawn if TTX-S is less sensitive to ketamine compared with TTX-R component even though it disappears later than TTX-R, which may be masked by significant reduction in TTX-S component by ketamine leading to less membrane depolarization up to the threshold for TTX-R, in this case, even if there is enough TTX-R available it would remain not to be activated, so the explanation from this observation will not be contradicted with literature [ 39 ]. From the cellular point of view, Ah-type afferents not only express similar ion channels compared with the C-type afferents, including TTX-S/TTX-R [ 18 , 27 ], KCa1.1 [ 28 , 43 ], and HCN1 [ 19 , 20 , 44 ], but also show identical chemosensitivity to histamine [ 24 , 25 ], so, it is not surprised that Ah-type afferents display a similar reaction to ketamine within presynaptic neurotransmission on the cell body and synaptic terminal of 1 st -order neurons as indicated in C-type afferents [ 4 ]. Although the effect of ketamine was not evaluated in the observation, the significant slow repolarization and broader AP duration suggested that certain K + channels must be blocked by ketamine, which is consistent with the previous documentation [ 40 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

“…Notably, the low-threshold and sex-specific distribution of myelinated Ah-type baroreceptor neurons (BRNs) [ 17 - 20 ] have extensively been studied since the intact nodose slice preparation is developed [ 21 , 22 ]. As compared with traditionally classified A- and C-types, the afferent conduction and neuroexcitability of this Ah-types are more like A-types, while, the afferent-specific chemosensitivity to vanilloid receptor agonist capsaicin [ 23 ] or neurotransmitter histamine [ 24 , 25 ] are more similar to A-types or C-types, respectively, which may lead at least partially to the sexual-dimorphism in aortic baroreflex function [ 26 ]. Even though Ah-types are fast conducted and myelinated afferents, they also share discharge characteristics with unmyelinated C-types, such as, repolarization hump [ 17 ], expression tetrodotoxin-resistant Na + channels [ 18 , 27 ], and large conductive Ca 2+ -activated K + channels [ 8 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Ketamine-mediated afferent-specific presynaptic transmission blocks in low-threshold and sex-specific subpopulation of myelinated Ah-type baroreceptor neurons of rats

et al. 2015

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BackgroundKetamine enhances autonomic activity, and unmyelinated C-type baroreceptor afferents are more susceptible to be blocked by ketamine than myelinated A-types. However, the presynaptic transmission block in low-threshold and sex-specific myelinated Ah-type baroreceptor neurons (BRNs) is not elucidated.MethodsAction potentials (APs) and excitatory post-synaptic currents (EPSCs) were investigated in BRNs/barosensitive neurons identified by conduction velocity (CV), capsaicin-conjugated with Iberiotoxin-sensitivity and fluorescent dye using intact nodose slice and brainstem slice in adult female rats. The expression of mRNA and targeted protein for NMDAR1 was also evaluated.ResultsKetamine time-dependently blocked afferent CV in Ah-types in nodose slice with significant changes in AP discharge. The concentration-dependent inhibition of ketamine on AP discharge profiles were also assessed and observed using isolated Ah-type BRNs with dramatic reduction in neuroexcitability. In brainstem slice, the 2nd-order capsaicin-resistant EPSCs were identified and ∼50% of them were blocked by ketamine concentration-dependently with IC50 estimated at 84.4 μM compared with the rest (708.2 μM). Interestingly, the peak, decay time constant, and area under curve of EPSCs were significantly enhanced by 100 nM iberiotoxin in ketamine-more sensitive myelinated NTS neurons (most likely Ah-types), rather than ketamine-less sensitive ones (A-types).ConclusionsThese data have demonstrated, for the first time, that low-threshold and sex-specific myelinated Ah-type BRNs in nodose and Ah-type barosensitive neurons in NTS are more susceptible to ketamine and may play crucial roles in not only mean blood pressure regulation but also buffering dynamic changes in pressure, as well as the ketamine-mediated cardiovascular dysfunction through sexual-dimorphic baroreflex afferent pathway.

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“…Female hormones, such as estrogen, can modulate the inflammatory response, and histamine receptors can differ between males and females, which might explain the different incidence of allergy between the sexes [ 31 ]. For example, H2R and H3R are highly expressed in female compared to male rats and are downregulated in ovariectomized females, whereas H1R is equally expressed in both sexes [ 32 ].…”

Section: Histamine and Histamine Receptorsmentioning

confidence: 99%

Role of Histamine in Modulating the Immune Response and Inflammation

Branco

Yoshikawa

Pietrobon

et al. 2018

Mediators of Inflammation

249

187

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Inflammatory mediators, including cytokines, histamine, bradykinin, prostaglandins, and leukotrienes, impact the immune system, usually as proinflammatory factors. Other mediators act as regulatory components to establish homeostasis after injury or prevent the inflammatory process. Histamine, a biogenic vasoactive amine, causes symptoms such as allergies and has a pleiotropic effect that is dependent on its interaction with its four histamine receptors. In this review, we discuss the dualistic effects of histamine: how histamine affects inflammation of the immune system through the activation of intracellular pathways that induce the production of inflammatory mediators and cytokines in different immune cells and how histamine exerts regulatory functions in innate and adaptive immune responses. We also evaluate the interactions between these effects.

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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

Cited by 27 publications

References 37 publications

Unique Expression of Angiotensin Type-2 Receptor in Sex-Specific Distribution of Myelinated Ah-Type Baroreceptor Neuron Contributing to Sex-Dimorphic Neurocontrol of Circulation

Unique Expression of Angiotensin Type-2 Receptor in Sex-Specific Distribution of Myelinated Ah-Type Baroreceptor Neuron Contributing to Sex-Dimorphic Neurocontrol of Circulation

Ketamine-mediated afferent-specific presynaptic transmission blocks in low-threshold and sex-specific subpopulation of myelinated Ah-type baroreceptor neurons of rats

Role of Histamine in Modulating the Immune Response and Inflammation

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