Blood oxygen regulation via P2Y12R expressed in the carotid body
Abstract Background Peripheral blood oxygen monitoring via chemoreceptors in the carotid body (CB) is an integral function of the autonomic cardiorespiratory regulation. The presence of the purinergic P2Y12 receptor (P2Y12R) has been implicated in CB; however, the exact role of the receptor in O2 se...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12931-024-02680-x |
| _version_ | 1797276370625101824 |
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| author | András Iring Mária Baranyi Bernadett Iring-Varga Paula Mut-Arbona Zsuzsanna T. Gál Dorina Nagy László Hricisák János Varga Zoltán Benyó Beáta Sperlágh |
| author_facet | András Iring Mária Baranyi Bernadett Iring-Varga Paula Mut-Arbona Zsuzsanna T. Gál Dorina Nagy László Hricisák János Varga Zoltán Benyó Beáta Sperlágh |
| author_sort | András Iring |
| collection | DOAJ |
| description | Abstract Background Peripheral blood oxygen monitoring via chemoreceptors in the carotid body (CB) is an integral function of the autonomic cardiorespiratory regulation. The presence of the purinergic P2Y12 receptor (P2Y12R) has been implicated in CB; however, the exact role of the receptor in O2 sensing and signal transduction is unknown. Methods The presence of P2Y12R was established by immunoblotting, RT qPCR and immunohistochemistry. Primary glomus cells were used to assess P2Y12R function during hypoxia and hypercapnia, where monoamines were measured by HPLC; calcium signal was recorded utilizing OGB-1 and N-STORM Super-Resolution System. Ingravescent hypoxia model was tested in anaesthetized mice of mixed gender and cardiorespiratory parameters were recorded in control and receptor-deficient or drug-treated experimental animals. Results Initially, the expression of P2Y12R in adult murine CB was confirmed. Hypoxia induced a P2Y12R-dependent release of monoamine transmitters from isolated CB cells. Receptor activation with the endogenous ligand ADP promoted release of neurotransmitters under normoxic conditions, while blockade disrupted the amplitude and duration of the intracellular calcium concentration. In anaesthetised mice, blockade of P2Y12R expressed in the CB abrogated the initiation of compensatory cardiorespiratory changes in hypoxic environment, while centrally inhibited receptors (i.e. microglial receptors) or receptor-deficiency induced by platelet depletion had limited influence on the physiological adjustment to hypoxia. Conclusions Peripheral P2Y12R inhibition interfere with the complex mechanisms of acute oxygen sensing by influencing the calcium signalling and the release of neurotransmitter molecules to evoke compensatory response to hypoxia. Prospectively, the irreversible blockade of glomic receptors by anti-platelet drugs targeting P2Y12Rs, propose a potential, formerly unrecognized side-effect to anti-platelet medications in patients with pulmonary morbidities. |
| first_indexed | 2024-03-07T15:27:19Z |
| format | Article |
| id | doaj.art-ee730e58e3444a448cc7d170b40305a3 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-03-07T15:27:19Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-ee730e58e3444a448cc7d170b40305a32024-03-05T16:39:15ZengBMCRespiratory Research1465-993X2024-01-0125112010.1186/s12931-024-02680-xBlood oxygen regulation via P2Y12R expressed in the carotid bodyAndrás Iring0Mária Baranyi1Bernadett Iring-Varga2Paula Mut-Arbona3Zsuzsanna T. Gál4Dorina Nagy5László Hricisák6János Varga7Zoltán Benyó8Beáta Sperlágh9Laboratory of Molecular Pharmacology, HUN-REN Institute of Experimental MedicineLaboratory of Molecular Pharmacology, HUN-REN Institute of Experimental MedicineLaboratory of Molecular Pharmacology, HUN-REN Institute of Experimental MedicineLaboratory of Molecular Pharmacology, HUN-REN Institute of Experimental MedicineLaboratory of Molecular Pharmacology, HUN-REN Institute of Experimental MedicineInstitute of Translational Medicine, Semmelweis UniversityInstitute of Translational Medicine, Semmelweis UniversityDepartment of Pulmonology, Faculty of Medicine, Semmelweis UniversityInstitute of Translational Medicine, Semmelweis UniversityLaboratory of Molecular Pharmacology, HUN-REN Institute of Experimental MedicineAbstract Background Peripheral blood oxygen monitoring via chemoreceptors in the carotid body (CB) is an integral function of the autonomic cardiorespiratory regulation. The presence of the purinergic P2Y12 receptor (P2Y12R) has been implicated in CB; however, the exact role of the receptor in O2 sensing and signal transduction is unknown. Methods The presence of P2Y12R was established by immunoblotting, RT qPCR and immunohistochemistry. Primary glomus cells were used to assess P2Y12R function during hypoxia and hypercapnia, where monoamines were measured by HPLC; calcium signal was recorded utilizing OGB-1 and N-STORM Super-Resolution System. Ingravescent hypoxia model was tested in anaesthetized mice of mixed gender and cardiorespiratory parameters were recorded in control and receptor-deficient or drug-treated experimental animals. Results Initially, the expression of P2Y12R in adult murine CB was confirmed. Hypoxia induced a P2Y12R-dependent release of monoamine transmitters from isolated CB cells. Receptor activation with the endogenous ligand ADP promoted release of neurotransmitters under normoxic conditions, while blockade disrupted the amplitude and duration of the intracellular calcium concentration. In anaesthetised mice, blockade of P2Y12R expressed in the CB abrogated the initiation of compensatory cardiorespiratory changes in hypoxic environment, while centrally inhibited receptors (i.e. microglial receptors) or receptor-deficiency induced by platelet depletion had limited influence on the physiological adjustment to hypoxia. Conclusions Peripheral P2Y12R inhibition interfere with the complex mechanisms of acute oxygen sensing by influencing the calcium signalling and the release of neurotransmitter molecules to evoke compensatory response to hypoxia. Prospectively, the irreversible blockade of glomic receptors by anti-platelet drugs targeting P2Y12Rs, propose a potential, formerly unrecognized side-effect to anti-platelet medications in patients with pulmonary morbidities.https://doi.org/10.1186/s12931-024-02680-xChemoreceptorHypoxiaO2 sensingPurinergic signallingSignal transductionCardiorespiratory regulation |
| spellingShingle | András Iring Mária Baranyi Bernadett Iring-Varga Paula Mut-Arbona Zsuzsanna T. Gál Dorina Nagy László Hricisák János Varga Zoltán Benyó Beáta Sperlágh Blood oxygen regulation via P2Y12R expressed in the carotid body Respiratory Research Chemoreceptor Hypoxia O2 sensing Purinergic signalling Signal transduction Cardiorespiratory regulation |
| title | Blood oxygen regulation via P2Y12R expressed in the carotid body |
| title_full | Blood oxygen regulation via P2Y12R expressed in the carotid body |
| title_fullStr | Blood oxygen regulation via P2Y12R expressed in the carotid body |
| title_full_unstemmed | Blood oxygen regulation via P2Y12R expressed in the carotid body |
| title_short | Blood oxygen regulation via P2Y12R expressed in the carotid body |
| title_sort | blood oxygen regulation via p2y12r expressed in the carotid body |
| topic | Chemoreceptor Hypoxia O2 sensing Purinergic signalling Signal transduction Cardiorespiratory regulation |
| url | https://doi.org/10.1186/s12931-024-02680-x |
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