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Thermoregulatory pathway underlying the pyrogenic effects of prostaglandin E 2 in the lateral parabrachial nucleus of male rats.

التفاصيل البيبلوغرافية
العنوان: Thermoregulatory pathway underlying the pyrogenic effects of prostaglandin E 2 in the lateral parabrachial nucleus of male rats.
المؤلفون: Xu JH; Key Laboratory of Thermoregulation and Inflammation of Sichuan Higher Education Institutes, Chengdu Medical College, Chengdu, 610500, China., He TH; Key Laboratory of Thermoregulation and Inflammation of Sichuan Higher Education Institutes, Chengdu Medical College, Chengdu, 610500, China., Wang NP; Key Laboratory of Thermoregulation and Inflammation of Sichuan Higher Education Institutes, Chengdu Medical College, Chengdu, 610500, China., Gao WM; Key Laboratory of Thermoregulation and Inflammation of Sichuan Higher Education Institutes, Chengdu Medical College, Chengdu, 610500, China., Cheng YJ; Key Laboratory of Thermoregulation and Inflammation of Sichuan Higher Education Institutes, Chengdu Medical College, Chengdu, 610500, China., Ji QF; Key Laboratory of Thermoregulation and Inflammation of Sichuan Higher Education Institutes, Chengdu Medical College, Chengdu, 610500, China., Wu SH; School of Clinical Medicine, Chengdu Medical College, Chengdu, 610500, China., Wei YL; School of Clinical Medicine, Chengdu Medical College, Chengdu, 610500, China., Tang Y; Key Laboratory of Thermoregulation and Inflammation of Sichuan Higher Education Institutes, Chengdu Medical College, Chengdu, 610500, China., Yang WZ; School of Life Science and Technology, Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, 201210, China. yangwen@shanghaitech.edu.cn., Zhang J; Key Laboratory of Thermoregulation and Inflammation of Sichuan Higher Education Institutes, Chengdu Medical College, Chengdu, 610500, China. zhangjiefa8888@126.com.
المصدر: Acta pharmacologica Sinica [Acta Pharmacol Sin] 2024 Sep; Vol. 45 (9), pp. 1832-1847. Date of Electronic Publication: 2024 May 03.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: United States NLM ID: 100956087 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1745-7254 (Electronic) Linking ISSN: 16714083 NLM ISO Abbreviation: Acta Pharmacol Sin Subsets: MEDLINE
أسماء مطبوعة: Publication: 2009- : New York : Nature Publishing Group
Original Publication: Beijing, China : Science Press, c2000-
مواضيع طبية MeSH: Body Temperature Regulation*/drug effects , Dinoprostone*/pharmacology , Fever*/chemically induced , Fever*/metabolism , Parabrachial Nucleus*/drug effects , Parabrachial Nucleus*/physiology , Preoptic Area*/drug effects , Preoptic Area*/metabolism , Receptors, Prostaglandin E, EP3 Subtype*/metabolism, Animals ; Male ; Rats ; Neurons/drug effects ; Neurons/metabolism ; Rats, Sprague-Dawley
مستخلص: It has been shown that prostaglandin (PG) E 2 synthesized in the lateral parabrachial nucleus (LPBN) is involved in lipopolysaccharide-induced fever. But the neural mechanisms of how intra-LPBN PGE 2 induces fever remain unclear. In this study, we investigated whether the LPBN-preoptic area (POA) pathway, the thermoafferent pathway for feed-forward thermoregulatory responses, mediates fever induced by intra-LPBN PGE 2 in male rats. The core temperature (T core ) was monitored using a temperature radiotelemetry transponder implanted in rat abdomen. We showed that microinjection of PGE 2 (0.28 nmol) into the LPBN significantly enhanced the density of c-Fos-positive neurons in the median preoptic area (MnPO). The chemical lesioning of MnPO with ibotenate or selective genetic lesioning or inhibition of the LPBN-MnPO pathway significantly attenuated fever induced by intra-LPBN injection of PGE 2 . We demonstrated that EP3 receptor was a pivotal receptor for PGE 2 -induced fever, since microinjection of EP3 receptor agonist sulprostone (0.2 nmol) or EP3 receptor antagonist L-798106 (2 nmol) into the LPBN mimicked or weakened the pyrogenic action of LPBN PGE 2 , respectively, but this was not the case for EP4 and EP1 receptors. Whole-cell recording from acute LPBN slices revealed that the majority of MnPO-projecting neurons originating from the external lateral (el) and dorsal (d) LPBN were excited and inhibited, respectively, by PGE 2 perfusion, initiating heat-gain and heat-loss mechanisms. The amplitude but not the frequency of spontaneous and miniature glutamatergic excitatory postsynaptic currents (sEPSCs and mEPSCs) in MnPO-projecting LPBel neurons increased after perfusion with PGE 2 ; whereas the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) and the A-type potassium (I A ) current density did not change. In MnPO-projecting LPBd neurons, neither sEPSCs nor sIPSCs responded to PGE 2 ; however, the I A current density was significantly increased by PGE 2 perfusion. These electrophysiological responses and the thermoeffector reactions to intra-LPBN PGE 2 injection, including increased brown adipose tissue thermogenesis, shivering, and decreased heat dissipation, were all abolished by L-798106, and mimicked by sulprostone. These results suggest that the pyrogenic effects of intra-LPBN PGE 2 are mediated by both the inhibition of the LPBd-POA pathway through the EP3 receptor-mediated activation of I A currents and the activation of the LPBel-POA pathway through the selective enhancement of glutamatergic synaptic transmission via EP3 receptors.
(© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)
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معلومات مُعتمدة: I01 CX002022 United States CX CSRD VA
فهرسة مساهمة: Keywords: A-type potassium current; EP3 receptor; PGE2; fever; lateral parabrachial nucleus; preoptic area
المشرفين على المادة: K7Q1JQR04M (Dinoprostone)
0 (Receptors, Prostaglandin E, EP3 Subtype)
0 (5-bromo-2-methoxy-N-(3-(naphthalen-2-yl-methylphenyl)acryloyl)benzenesulfonamide)
تواريخ الأحداث: Date Created: 20240503 Date Completed: 20240820 Latest Revision: 20240823
رمز التحديث: 20240823
مُعرف محوري في PubMed: PMC11336216
DOI: 10.1038/s41401-024-01289-6
PMID: 38702500
قاعدة البيانات: MEDLINE
الوصف
تدمد:1745-7254
DOI:10.1038/s41401-024-01289-6