Adrenomedullin-mediated depressor response with visceral afferent-specific membrane depolarization in isolated nodose ganglion neurons from adult female rat

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides Pub Date : 2024-10-10 DOI:10.1016/j.npep.2024.102476

Yan Feng , Ying Li , Hua Liu

{"title":"Adrenomedullin-mediated depressor response with visceral afferent-specific membrane depolarization in isolated nodose ganglion neurons from adult female rat","authors":"Yan Feng , Ying Li , Hua Liu","doi":"10.1016/j.npep.2024.102476","DOIUrl":null,"url":null,"abstract":"<div><div>Adrenomedullin (ADM) is an endogenous and vasoactive neuropeptide that possesses potent central/peripheral regulations on blood pressure (BP) and sex-related vasodilation under physiological conditions. However, the role of ADM on baroreflex afferent function is largely unknown. Here, BP was monitored in adult female rats while ADM was microinjected into the nodose ganglion (NG); Fluorescent intensity against ADM was analyzed in the tissue level and membrane responses elicited by ADM were tested in identified NG neurons isolated from adult female rats with gap-free protocol under current-clamp mode with or without ADM antagonist. The results showed that BP was reduced by ADM (30–300 nM) concentration-dependently; myelinated (HCN1-positive) neurons showed significantly higher fluorescent intensity against ADM antibody vs. unmyelinated (HCN1-negative) neurons. Interestingly, patch-clamp data indicated that membrane potential was not changed in 50 % (6/12) of identified A-types, only 4/12 was hyperpolarized by 30 nM ADM, while 100 nM ADM induced brief hyperpolarization followed by depolarization in 2/12 of recordings; Robustly, ADM depolarized 100 % tested myelinated Ah-type neurons with dramatic and concentration-dependent repetitive discharges; While, a majority (8/9) of unmyelinated C-types were depolarized and few with repetitive dischargers. By application of ADM (22–52), the depolarization elicited by ADM 100 nM was partially or completely abolished in Ah-types or C-types, respectively. These datasets demonstrated for the first time that baroreflex afferents especially female-distributed subpopulation of Ah-types would be a key player in ADM-mediated depressor response unveiling the dominate role of peripheral ADM in neurocontrol of hypotension via baroreflex afferent function and gender-dependent vasodilation promoted by female sex steroid.</div></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":"108 ","pages":"Article 102476"},"PeriodicalIF":2.5000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuropeptides","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0143417924000751","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

Abstract

Adrenomedullin (ADM) is an endogenous and vasoactive neuropeptide that possesses potent central/peripheral regulations on blood pressure (BP) and sex-related vasodilation under physiological conditions. However, the role of ADM on baroreflex afferent function is largely unknown. Here, BP was monitored in adult female rats while ADM was microinjected into the nodose ganglion (NG); Fluorescent intensity against ADM was analyzed in the tissue level and membrane responses elicited by ADM were tested in identified NG neurons isolated from adult female rats with gap-free protocol under current-clamp mode with or without ADM antagonist. The results showed that BP was reduced by ADM (30–300 nM) concentration-dependently; myelinated (HCN1-positive) neurons showed significantly higher fluorescent intensity against ADM antibody vs. unmyelinated (HCN1-negative) neurons. Interestingly, patch-clamp data indicated that membrane potential was not changed in 50 % (6/12) of identified A-types, only 4/12 was hyperpolarized by 30 nM ADM, while 100 nM ADM induced brief hyperpolarization followed by depolarization in 2/12 of recordings; Robustly, ADM depolarized 100 % tested myelinated Ah-type neurons with dramatic and concentration-dependent repetitive discharges; While, a majority (8/9) of unmyelinated C-types were depolarized and few with repetitive dischargers. By application of ADM (22–52), the depolarization elicited by ADM 100 nM was partially or completely abolished in Ah-types or C-types, respectively. These datasets demonstrated for the first time that baroreflex afferents especially female-distributed subpopulation of Ah-types would be a key player in ADM-mediated depressor response unveiling the dominate role of peripheral ADM in neurocontrol of hypotension via baroreflex afferent function and gender-dependent vasodilation promoted by female sex steroid.

查看原文本刊更多论文

成年雌鼠离体结节神经元中肾上腺髓质素介导的内脏传入特异性膜去极化抑制反应

肾上腺髓质素（ADM）是一种具有血管活性的内源性神经肽，在生理条件下对血压（BP）和与性别相关的血管扩张具有强有力的中枢/外周调节作用。然而，ADM 对气压反射传入功能的作用在很大程度上是未知的。在此，研究人员向成年雌性大鼠的结节神经节（NG）微注射了ADM，同时监测了大鼠的血压；在组织水平分析了针对ADM的荧光强度，并在电流钳模式下使用或不使用ADM拮抗剂，通过无间隙方案检测了从成年雌性大鼠身上分离出的NG神经元中ADM引起的膜反应。结果表明，ADM（30-300 nM）浓度依赖性地降低了血压；与无髓鞘（HCN1 阴性）神经元相比，有髓鞘（HCN1 阳性）神经元对 ADM 抗体的荧光强度明显更高。有趣的是，膜片钳数据显示，50%（6/12）的已识别 A 型神经元的膜电位没有发生变化，只有 4/12 的神经元在 30 nM ADM 的作用下发生超极化，而在 2/12 的记录中，100 nM ADM 会诱导短暂的超极化，随后发生去极化；ADM能使100%接受测试的有髓鞘的AH型神经元去极化，并产生显著的、浓度依赖性的重复放电；而大多数（8/9）无髓鞘的C型神经元去极化，只有极少数产生重复放电。应用 ADM（22-52）后，Ah 型或 C 型神经元分别部分或完全消除了 ADM 100 nM 引起的去极化。这些数据集首次证明了气压反射传入，尤其是雌性分布的 Ah 型亚群在 ADM 介导的降压反应中起着关键作用，揭示了外周 ADM 通过气压反射传入功能和雌性激素促进的性别依赖性血管扩张在低血压神经控制中的主导作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Neuropeptides 医学-内分泌学与代谢

CiteScore

5.40

自引率

6.90%

发文量

审稿时长

>12 weeks

期刊介绍： The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems. The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.