Prostaglandin E2 Exerts Biphasic Dose Response on the PreBötzinger Complex Respiratory-Related Rhythm
Inflammation in infants can cause respiratory dysfunction and is potentially life-threatening. Prostaglandin E2 (PGE2) is released during inflammatory events and perturbs breathing behavior in vivo. Here we study the effects of PGE2 on inspiratory motor rhythm generated by the preBötzinger complex (...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Neural Circuits |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncir.2022.826497/full |
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| author | Jan Philipp Reising Jan Philipp Reising Wiktor S. Phillips Wiktor S. Phillips Naify Ramadan Naify Ramadan Eric Herlenius Eric Herlenius |
| author_facet | Jan Philipp Reising Jan Philipp Reising Wiktor S. Phillips Wiktor S. Phillips Naify Ramadan Naify Ramadan Eric Herlenius Eric Herlenius |
| author_sort | Jan Philipp Reising |
| collection | DOAJ |
| description | Inflammation in infants can cause respiratory dysfunction and is potentially life-threatening. Prostaglandin E2 (PGE2) is released during inflammatory events and perturbs breathing behavior in vivo. Here we study the effects of PGE2 on inspiratory motor rhythm generated by the preBötzinger complex (preBötC). We measured the concentration dependence of PGE2 (1 nM-1 μM) on inspiratory-related motor output in rhythmic medullary slice preparations. Low concentrations (1–10 nM) of PGE2 increased the duration of the inspiratory burst period, while higher concentrations (1 μM) decreased the burst period duration. Using specific pharmacology for prostanoid receptors (EP1-4R, FPR, and DP2R), we determined that coactivation of both EP2R and EP3R is necessary for PGE2 to modulate the inspiratory burst period. Additionally, biased activation of EP3 receptors lengthened the duration of the inspiratory burst period, while biased activation of EP2 receptors shortened the burst period. To help delineate which cell populations are affected by exposure to PGE2, we analyzed single-cell RNA-Seq data derived from preBötC cells. Transcripts encoding for EP2R (Ptger2) were differentially expressed in a cluster of excitatory neurons putatively located in the preBötC. A separate cluster of mixed inhibitory neurons differentially expressed EP3R (Ptger3). Our data provide evidence that EP2 and EP3 receptors increase the duration of the inspiratory burst period at 1–10 nM PGE2 and decrease the burst period duration at 1 μM. Further, the biphasic dose response likely results from differences in receptor binding affinity among prostanoid receptors. |
| first_indexed | 2024-04-13T17:28:11Z |
| format | Article |
| id | doaj.art-d62627a6868b421a8ced13c84997d858 |
| institution | Directory Open Access Journal |
| issn | 1662-5110 |
| language | English |
| last_indexed | 2024-04-13T17:28:11Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neural Circuits |
| spelling | doaj.art-d62627a6868b421a8ced13c84997d8582022-12-22T02:37:41ZengFrontiers Media S.A.Frontiers in Neural Circuits1662-51102022-05-011610.3389/fncir.2022.826497826497Prostaglandin E2 Exerts Biphasic Dose Response on the PreBötzinger Complex Respiratory-Related RhythmJan Philipp Reising0Jan Philipp Reising1Wiktor S. Phillips2Wiktor S. Phillips3Naify Ramadan4Naify Ramadan5Eric Herlenius6Eric Herlenius7Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, SwedenAstrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, SwedenDepartment of Women’s and Children’s Health, Karolinska Institutet, Stockholm, SwedenAstrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, SwedenDepartment of Women’s and Children’s Health, Karolinska Institutet, Stockholm, SwedenAstrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, SwedenDepartment of Women’s and Children’s Health, Karolinska Institutet, Stockholm, SwedenAstrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, SwedenInflammation in infants can cause respiratory dysfunction and is potentially life-threatening. Prostaglandin E2 (PGE2) is released during inflammatory events and perturbs breathing behavior in vivo. Here we study the effects of PGE2 on inspiratory motor rhythm generated by the preBötzinger complex (preBötC). We measured the concentration dependence of PGE2 (1 nM-1 μM) on inspiratory-related motor output in rhythmic medullary slice preparations. Low concentrations (1–10 nM) of PGE2 increased the duration of the inspiratory burst period, while higher concentrations (1 μM) decreased the burst period duration. Using specific pharmacology for prostanoid receptors (EP1-4R, FPR, and DP2R), we determined that coactivation of both EP2R and EP3R is necessary for PGE2 to modulate the inspiratory burst period. Additionally, biased activation of EP3 receptors lengthened the duration of the inspiratory burst period, while biased activation of EP2 receptors shortened the burst period. To help delineate which cell populations are affected by exposure to PGE2, we analyzed single-cell RNA-Seq data derived from preBötC cells. Transcripts encoding for EP2R (Ptger2) were differentially expressed in a cluster of excitatory neurons putatively located in the preBötC. A separate cluster of mixed inhibitory neurons differentially expressed EP3R (Ptger3). Our data provide evidence that EP2 and EP3 receptors increase the duration of the inspiratory burst period at 1–10 nM PGE2 and decrease the burst period duration at 1 μM. Further, the biphasic dose response likely results from differences in receptor binding affinity among prostanoid receptors.https://www.frontiersin.org/articles/10.3389/fncir.2022.826497/fullpreBötzinger complex (preBötC)prostaglandin E2 (PGE2)inflammationneural networksrespiratory – mechanics |
| spellingShingle | Jan Philipp Reising Jan Philipp Reising Wiktor S. Phillips Wiktor S. Phillips Naify Ramadan Naify Ramadan Eric Herlenius Eric Herlenius Prostaglandin E2 Exerts Biphasic Dose Response on the PreBötzinger Complex Respiratory-Related Rhythm Frontiers in Neural Circuits preBötzinger complex (preBötC) prostaglandin E2 (PGE2) inflammation neural networks respiratory – mechanics |
| title | Prostaglandin E2 Exerts Biphasic Dose Response on the PreBötzinger Complex Respiratory-Related Rhythm |
| title_full | Prostaglandin E2 Exerts Biphasic Dose Response on the PreBötzinger Complex Respiratory-Related Rhythm |
| title_fullStr | Prostaglandin E2 Exerts Biphasic Dose Response on the PreBötzinger Complex Respiratory-Related Rhythm |
| title_full_unstemmed | Prostaglandin E2 Exerts Biphasic Dose Response on the PreBötzinger Complex Respiratory-Related Rhythm |
| title_short | Prostaglandin E2 Exerts Biphasic Dose Response on the PreBötzinger Complex Respiratory-Related Rhythm |
| title_sort | prostaglandin e2 exerts biphasic dose response on the prebotzinger complex respiratory related rhythm |
| topic | preBötzinger complex (preBötC) prostaglandin E2 (PGE2) inflammation neural networks respiratory – mechanics |
| url | https://www.frontiersin.org/articles/10.3389/fncir.2022.826497/full |
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