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Il-1β and prostaglandin E2 attenuate the hypercapnic as well as the hypoxic respiratory response via prostaglandin E receptor type 3 in neonatal mice.

Authors
  • Siljehav, Veronica
  • Shvarev, Yuri
  • Herlenius, Eric
Type
Published Article
Journal
Journal of Applied Physiology
Publisher
American Physiological Society
Publication Date
Nov 01, 2014
Volume
117
Issue
9
Pages
1027–1036
Identifiers
DOI: 10.1152/japplphysiol.00542.2014
PMID: 25213632
Source
Medline
Keywords
License
Unknown

Abstract

Prostaglandin E2 (PGE2) serves as a critical mediator of hypoxia, infection, and apnea in term and preterm babies. We hypothesized that the prostaglandin E receptor type 3 (EP3R) is the receptor responsible for PGE2-induced apneas. Plethysmographic recordings revealed that IL-1β (ip) attenuated the hypercapnic response in C57BL/6J wild-type (WT) but not in neonatal (P9) EP3R(-/-) mice (P < 0.05). The hypercapnic responses in brain stem spinal cord en bloc preparations also differed depending on EP3R expression whereby the response was attenuated in EP3R(-/-) preparations (P < 0.05). After severe hypoxic exposure in vivo, IL-1β prolonged time to autoresuscitation in WT but not in EP3R(-/-) mice. Moreover, during severe hypoxic stress EP3R(-/-) mice had an increased gasping duration (P < 0.01) as well as number of gasps (P < 0.01), irrespective of intraperitoneal treatment, compared with WT mice. Furthermore, EP3R(-/-) mice exhibited longer hyperpneic breathing efforts when exposed to severe hypoxia (P < 0.01). This was then followed by a longer period of secondary apnea before autoresuscitation occurred in EP3R(-/-) mice (P < 0.05). In vitro, EP3R(-/-) brain stem spinal cord preparations had a prolonged respiratory burst activity during severe hypoxia accompanied by a prolonged neuronal arrest during recovery in oxygenated medium (P < 0.05). In conclusion, PGE2 exerts its effects on respiration via EP3R activation that attenuates the respiratory response to hypercapnia as well as severe hypoxia. Modulation of the EP3R may serve as a potential therapeutic target for treatment of inflammatory and hypoxic-induced detrimental apneas and respiratory disorders in neonates.

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