μ-阿片类药物受体(MORs)负责介导阿片类药物的镇痛和呼吸作用。通过与控制呼吸的脑干区域的MORs结合,阿片类药物产生呼吸抑制作用,其特征是缓慢和浅呼吸,在用药过量时可能导致心肺骤停和死亡。为了更好地了解阿片类药物引起的呼吸抑制的潜在机制,需要全面了解可能易受阿片类药物调节的区域和细胞亚群。使用原位杂交,我们测定了Oprm1(编码MORs的基因)mRNA与谷氨酸能(Vglut2)和神经激肽-1受体(Tacr1)mRNA在参与呼吸控制和调节的髓质和脑桥区域的分布和共表达.我们发现,>50%的细胞在preBötzinger复合物(preBötC)中表达Oprm1mRNA,孤束核(NTS),模糊核(NA),蓝斑(LC),Kölliker-Fuse核(KF),以及外侧和内侧臂旁核(LBPN和MPBN,分别)。在Tacr1mRNA表达细胞中,>50%的Oprm1mRNA在preBötC共表达,NTS,NA,Bötzinger复合体(BötC),LC,中缝马格核,KF,LPBN,MPBN,而在Vglut2mRNA表达细胞中,>50%的Oprm1mRNA在preBötC共表达,NTS,NA,BötC,LC,KF,LPBN,MPBN一起来看,我们的研究提供了Oprm1,Tacr1和Vglut2mRNA在控制和调节呼吸的脑干区域的分布和共表达的全面图谱,并将表达Tacr1和Vglut2mRNA的细胞鉴定为可能易受阿片类药物调节的亚群.
µ-Opioid receptors (MORs) are responsible for mediating both the analgesic and respiratory effects of opioid drugs. By binding to MORs in brainstem regions involved in controlling breathing, opioids produce respiratory depressive effects characterized by slow and shallow breathing, with potential cardiorespiratory arrest and death during overdose. To better understand the mechanisms underlying opioid-induced respiratory depression, thorough knowledge of the regions and cellular subpopulations that may be vulnerable to modulation by opioid drugs is needed. Using in situ hybridization, we determined the distribution and coexpression of Oprm1 (gene encoding MORs) mRNA with glutamatergic (Vglut2) and neurokinin-1 receptor (Tacr1) mRNA in medullary and pontine regions involved in breathing control and modulation. We found that >50% of cells expressed Oprm1 mRNA in the preBötzinger complex (preBötC), nucleus tractus solitarius (NTS), nucleus ambiguus (NA), postinspiratory complex (PiCo), locus coeruleus (LC), Kölliker-Fuse nucleus (KF), and the lateral and medial parabrachial nuclei (LBPN and MPBN, respectively). Among Tacr1 mRNA-expressing cells, >50% coexpressed Oprm1 mRNA in the preBötC, NTS, NA, Bötzinger complex (BötC), PiCo, LC, raphe magnus nucleus, KF, LPBN, and MPBN, whereas among Vglut2 mRNA-expressing cells, >50% coexpressed Oprm1 mRNA in the preBötC, NTS, NA, BötC, PiCo, LC, KF, LPBN, and MPBN. Taken together, our study provides a comprehensive map of the distribution and coexpression of Oprm1, Tacr1, and Vglut2 mRNA in brainstem regions that control and modulate breathing and identifies Tacr1 and Vglut2 mRNA-expressing cells as subpopulations with potential vulnerability to modulation by opioid drugs.NEW & NOTEWORTHY Opioid drugs can cause serious respiratory side-effects by binding to µ-opioid receptors (MORs) in brainstem regions that control breathing. To better understand the regions and their cellular subpopulations that may be vulnerable to modulation by opioids, we provide a comprehensive map of Oprm1 (gene encoding MORs) mRNA expression throughout brainstem regions that control and modulate breathing. Notably, we identify glutamatergic and neurokinin-1 receptor-expressing cells as potentially vulnerable to modulation by opioid drugs and worthy of further investigation using targeted approaches.